CN108403766A - It is a kind of to treat drug-resistant bacteria disease composition and its preparation method and application - Google Patents

It is a kind of to treat drug-resistant bacteria disease composition and its preparation method and application Download PDF

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CN108403766A
CN108403766A CN201810555304.2A CN201810555304A CN108403766A CN 108403766 A CN108403766 A CN 108403766A CN 201810555304 A CN201810555304 A CN 201810555304A CN 108403766 A CN108403766 A CN 108403766A
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drug
thick paste
resistant bacteria
composition
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朱宇嘉
辛年香
朱盛山
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Guangzhou Universal Biotechnology Co Ltd
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Abstract

Drug-resistant bacteria disease composition and its preparation method and application is treated the present invention relates to a kind of.The composition includes following components of following weight parts:200-400 parts by weight of half of lotus flower, 100-300 parts by weight of radix scutellariae, 100-300 parts by weight of X, wherein X are one or more in Folium Loropetali, Vitex negundo var cannabifolia, elephants-foot, iron holly bark, cloves.The present composition uses the Chinese herbal medicines such as half of lotus flower, radix scutellariae as active ingredient, and helps with Folium Loropetali, Vitex negundo var cannabifolia, elephants-foot, iron holly bark, cloves etc., has the function of good antibacterial, improves immunity of organisms;Clearing heat and detoxicating, righting of getting rid of evils the work(of the existing Chinese medicine of the prescription compatibility of medicines, and have the antibacterial of modern medicine, desinsection, adjust the benefits of immune function, have effects that maintain intestinal health, is the good recipe for treating drug-resistant bacteria infectious diseases.

Description

It is a kind of to treat drug-resistant bacteria disease composition and its preparation method and application
Technical field
The present invention relates to field of Chinese medicinal composition, and in particular to a kind of to treat drug-resistant bacteria disease composition and preparation method thereof And application.
Background technology
Bacterial drug resistance (Resistance to Drug) is also known as drug resistance, and it is resistance to mean that bacterium acts on antibacterials By property, once generating, the Chemotherapy of drug is just decreased obviously drug resistance.In view of the bacterial drug resistance trend of current sternness, generation Boundary's health organization delivered in the world most drug resistance, can most threaten " superbacteria " of human health.According to degree of danger Difference can be divided into three classes:" serious fatal, height is fatal, moderate is fatal " three classes, specificity resists required for representing us The urgent degree of raw element.Likewise, being divided into 3 ranks to generating drug resistant bacterium extensively, wherein rank 1:Serious carbapenem Drug resistance Acinetobacter baumannii, Pseudomonas aeruginosa, enterobacteria;Rank 2:Height drug resistance dung enterobacteria (vancomycin-resistant); Staphylococcus aureus (methicillin, vancomycin-resistant);Helicobacter pylori (clarithromycin drug resistance);Campylobacter, Salmonella, gonococcus (mediated quinolone resistance);Rank 3:Medium drug resistance Diplococcus pneumopniae, haemophilus influenzae and will Hayes bacillus.Actually generated in reality drug resistant bacterium extensively be not classified it is other also have it is many, as tubercle bacillus, comma bacillus, Vibrio parahemolyticus, Vibrio vulnificus, enterobacter cloacae, escherichia coli etc..
The main reason for generating drug-fast bacteria is that drug-fast bacteria generates inactivation (passivation) enzyme, antibacterials target site changes, changes Become bacterium outer membrane permeability, the formation of bacterial biofilm, cross resistance etc..The unreasonable of antibacterials uses and excessively makes The main reason for being microorganism drug resistance.It is reported that 2000 to 2010 years, the Antibiogics usage amount for the mankind increases 36%.The antibacterials for the treatment of infected animal are originally used for, are but widely used in agricultural, fish and marine product in many countries Cultivation, accelerating agent or prevention disease as growth of animal.The World Health Organization (WHO) points out developed country and developing country There are more and more people to infect " superbacteria " that existing method can not treat.Every year, global about 700,000 people die of drug-fast bacteria Infection, it is most of in developing country;Nearest estimation number shows that the year two thousand fifty, this number may rise to 1000 Ten thousand, it is more than current number of cancer deaths.
Abuse of antibiotics not only seriously affects human health, also results in economic loss.Bacterial resistance has become the whole world Severe public health problem, drug resistance enterobacteria, Klebsiella Pneumoniae, staphylococcus aureus, Salmonella, dung intestines ball Bacterium and Shiga bacillus etc. and tubercle bacillus, comma bacillus, vibrio parahemolyticus, Vibrio vulnificus etc. all have big drug resistance Property and difficulty it is treated.More refractory more abuse of antibiotics, more abuse of antibiotics, drug resistance bacterium is more, and problem is more serious, when Carve the health for endangering the mankind.
Invention content
In view of this, it is necessary to be directed to above-mentioned problem, provide and a kind for the treatment of drug-resistant bacteria disease composition and its preparation side Method and application.
Above-mentioned purpose of the present invention is achieved by following technology:
A kind of to treat drug-resistant bacteria disease composition, it includes following components of following weight parts:Half of lotus flower 200-400 Parts by weight, 100-300 parts by weight of radix scutellariae, 100-300 parts by weight of X, wherein X is Folium Loropetali, Vitex negundo var cannabifolia, elephants-foot, rescue must It answers, is in cloves one or more.
Preferably, the composition also includes 200-700 parts by weight of auxiliary material, and the auxiliary material is one in dextrin, glucose Kind is a variety of.
The present invention also provides a kind of preparation methods for treating drug-resistant bacteria disease composition comprising following steps:
S1, the mixture 2 times that half of lotus flower and radix scutellariae are extracted with ethanol solution, it is 1-2 hour each, merge after filtering and filters Liquid, and be concentrated under reduced pressure into thick paste A at 60-80 DEG C, wherein a concentration of the 75% of extraction ethanol solution used every time, every time The weight of extraction ethanol solution used is 10-20 times of the total weight of the mixture of the half of lotus flower and radix scutellariae;
S2, it is extracted X2 times, 1-2 hours each, merging filtrate after filtering, and depressurized at 60-80 DEG C dense with ethanol solution Shorten thick paste B into, wherein extract a concentration of the 50% of ethanol solution used for the first time, second of extraction ethanol solution used A concentration of 30%, 8-12 times of the weight that the weight of extraction ethanol solution used is X every time, the X for selected from Folium Loropetali, It is one or more in Vitex negundo var cannabifolia, elephants-foot, iron holly bark, cloves;
S3, the thick paste A is merged with the thick paste B, obtains thick paste C;And
S4, by the thick paste C and auxiliaries at the treatment drug-resistant bacteria disease composition.
Preferably, step S4 includes that the thick paste C is added in the auxiliary material, wet granular is made through granulator after stirring evenly, so It is dry at 60-80 DEG C afterwards, whole grain, packing, sealing, with the drug-resistant bacteria disease composition granule that obtains medical treatment.
Preferably, the step S1) described in thick paste A weight be the half of lotus flower and radix scutellariae mixture gross weight The 1/3-2/3 of amount;The step S2) described in thick paste B weight be the X total weight 1/4-1/2;The step S3) Described in thick paste C weight be the half of lotus flower, the radix scutellariae and the X total weight 1/4-3/4.
The present invention also provides a kind of application of above-mentioned composition in preparing the drug for treating drug-resistant bacteria disease.
Further, the drug-resistant bacteria in the drug-resistant bacteria disease is drug resistance enterobacteria, Klebsiella Pneumoniae, golden yellow Staphylococcus, Salmonella, enterococcus faecium, Shiga bacillus, tubercle bacillus, comma bacillus, vibrio parahemolyticus or wound Vibrios.
Composition provided by the invention is using Chinese herbal medicines such as half of lotus flower, radix scutellariaes as active ingredient, wherein half of lotus flower Acrid flavour, mild-natured, the thoughts of returning home, small intestine, lung channel;Inducing diuresis to remove edema, it is clearing heat and detoxicating, it is used for extensive abdominal edema, face foot edema, carbuncle swells furunculosis, snake Insect bite;Modern times are used for antiulcer, control diarrhea effect;Radix scutellariae bitter, cold in nature, purging intense heat clearing damp, except damp and hot;Modern chemistry and pharmacology Learn research shows that:Radix scutellariae is to shigella dysenteriae, typhoid bacillus, comma bacillus, Escherichia coli, proteus, Pseudomonas aeruginosa, grape ball Bacterium, hemolytic vessel used to hold grain at the imperial sacrifice coccus (a, B) etc. have inhibiting effect.
Meanwhile helped in composition provided by the invention with Folium Loropetali, Vitex negundo var cannabifolia, elephants-foot, iron holly bark, cloves etc., Have the function of good antibacterial, improve immunity of organisms;Clearing heat and detoxicating, righting of getting rid of evils the work(of the existing Chinese medicine of the prescription compatibility of medicines, There is the antibacterial of modern medicine again, desinsection, adjust the benefits of immune function, have effects that maintain intestinal health, is that treatment drug resistance is thin The good recipe of bacterium infectious diseases has the function of good overriding resistance bacterial infection disease.
Specific implementation mode
In order to better illustrate the present invention, it is described further With reference to embodiment.Examination used in the present invention Agent or instrument are available on the market, and detection method used etc. is all known in the art, and details are not described herein.The present invention Operations and the conditions such as middle water carries, alcohol extracting, unless otherwise indicated, using the prior art.
The embodiment of the present invention offer is a kind of to treat drug-resistant bacteria disease composition, and it includes following groups of following weight parts Point:200-400 parts by weight of half of lotus flower, 100-300 parts by weight of radix scutellariae, 100-300 parts by weight of X, wherein X be Folium Loropetali, It is one or more in Vitex negundo var cannabifolia, elephants-foot, iron holly bark, cloves.
The drug effect of each ingredient in treatment drug-resistant bacteria disease composition provided by the invention is briefly discussed below:
Half of lotus flower
【Nature and flavor and channel tropism】It is sweet in flavor, mild-natured, the thoughts of returning home, lung, small intestinl channel.
【Effect】It is clearing heat and detoxicating;Inducing diuresis for removing edema.
【Pharmacological action】
1, bacteriostasis:Chinese lobelia decocting liquid tablet trench method, to staphylococcus aureus, shigella flexneri, typhoid fever Bacillus, Pseudomonas aeruginosa, Escherichia coli have inhibiting effect.
2, immunoregulation effect:Polysaccharide contained by this product can promote the mouse boosting cell lymphocyte that ConA is induced in vitro Conversion, optimum concentration 400r/ml.It is positive thin that 1 Zhou Houke of Sc administrations significantly improves esterase in Mouse Peripheral Blood Lymphocyte The percentage of born of the same parents promotes the delayed allergy of DNCB inductions.
Radix scutellariae
【Nature and flavor and channel tropism】Bitter, cold in nature, the thoughts of returning home, lung, courage, large intestine channel.
【Effect】Excess fire is rushed down, except damp and hot.
【Pharmacological action】
1, antibacterial action:To shigella dysenteriae, typhoid bacillus, paratyphosum Bacterium, comma bacillus, Escherichia coli, proteus, Pseudomonas aeruginosa, staphylococcus, hemolytic vessel used to hold grain at the imperial sacrifice coccus (a, B), Diplococcus pneumopniae, corynebacterium diphtheriae etc. have inhibiting effect.
2, antivirus action:Radix scutellariae decoction 25-100% concentration, in vitro test are replicated with inhibition to hepatitis B virus DNA Effect.
3, liver protection, cholagogic, antioxidation.
Folium Loropetali
【Nature and flavor and channel tropism】Bitter, it is puckery, it is cool in nature.Return liver, stomach, large intestine channel.
【Effect】It is clearing heat and detoxicating, it restrains, hemostasis.
【Pharmacological action】Antibacterial action:In vitro test has staphylococcus, streptococcus, typhoid fever and Escherichia coli etc. antibacterial Or bactericidal effect.Folium Loropetali mainly contains gallic acid, tannin, flavonoids (mainly Quercetin).Ethanol extract is to green pus Bacillus, shigella dysenteriae, proteus, Escherichia coli, typhoid bacillus, bacillus enteritidis, bacillus anthracis, corynebacterium diphtheriae, golden yellow Portugal It may be Coumarins and tannin that grape coccus, streptococcus, which have inhibiting effect, bacteriostatic active ingredients,.
Vitex negundo var cannabifolia
【Nature and flavor and channel tropism】It is bitter, cold in nature.It is distributed in lung channel.
【Effect】Inducing diaphoresis dampness elimination, eliminating phlegm and relieving asthma;Removing toxic substances, expels pathogenic wind from the body surface, and dehumidifies, desinsection, analgesic.
【Pharmacological action】
1, antibacterial action:Vitex negundo var cannabifolia cauline leaf water decoction has notable antibacterial to make staphylococcus aureus and bacillus anthracis in vitro With also thering is certain antibacterial to make Escherichia coli, beta streptococcus, corynebacterium diphtheriae, typhoid bacillus, green pus liver bacterium and shigella dysenteriae etc. With.
2, enhance body's immunity:Herba Viticis Cannabifoliae volatile oil 0.35ml/ (kgd) gavage, continuous 6d have enhancing abdominal cavity macrophage Trend of the cell to chicken red blood cell phagocytosis.Principal component cloves alkene can increase Serological IgG level, show there is enhancing humoral immunity Effect.
Elephants-foot
【Nature and flavor and channel tropism】It is bitter, cool in nature, return stomach, large intestine channel.
【Effect】It is clearing heat and detoxicating, inducing diuresis to remove edema, cool blood.
【Pharmacological action】
With stronger antibacterial action, decocting liquid and alcohol extract are to Escherichia coli, bacillus subtilis, golden yellow grape Coccus etc. is inhibited.It is usually used in various diseases associated with inflammation:Flu, acute tonsillitis, sphagitis, eye conjunctivitis, stream Row encephalitis B, pertussis, acute icteric hepatitis, cirrhotic ascites, acute and chronic ephritis, furuncle, eczema.
Iron holly bark
【Nature and flavor and channel tropism】Bitter, it is cool in nature.Return lung;Liver;Large intestine channel
【Effect】It is clearing heat and detoxicating, dampness removing, swelling and pain relieving.
【Pharmacological action】
1, antibacterial action:Decoction test tube interior energy inhibits staphylococcus aureus, hemolytic streptococcus and dysentery (Freund), wound Cold, Pseudomonas aeruginosa.
2, anastalsis and the influence to smooth muscle:Chemical composition bark divides containing glycosides displayed, phenols, tannin, Triterpene Glycosides Separate out rotundic acid
Cloves
【Nature and flavor and channel tropism】Property pungent, taste temperature, return lung, spleen, stomach, kidney four pass through.
【Effect】Middle benefit gas, warm kidney, drop are inverse.
【Pharmacological action】
1, antibacterial, antiviral:Caryophyllus oil and eugenol have the antibacterial action of wide spectrum.Ellagitannins in cloves has anti-simple Herpesviral acts on.
2, antimycotic:Its water decoction or alcohol leaching liquid have the antifungic action or killing effect of wide spectrum.Eugenol dialogue Color candida albicans and Cryptococcus neoformans have significant killing effect.
3, parasite is killed:Its water extract can kill dog and ascaris suum.The effect of caryophyllus oil is strong compared with the effect of water decoction.
4, trichomonad is killed:Caryophyllus oil, eugenol and aceteugenol have very strong killing effect to trichmonad.
Composition provided by the invention is using Chinese herbal medicines such as half of lotus flower, radix scutellariaes as active ingredient, wherein half of lotus flower Acrid flavour, mild-natured, the thoughts of returning home, small intestine, lung channel;Inducing diuresis to remove edema, it is clearing heat and detoxicating, it is used for extensive abdominal edema, face foot edema, carbuncle swells furunculosis, snake Insect bite;Modern times are used for antiulcer, control diarrhea effect;Radix scutellariae bitter, cold in nature, purging intense heat clearing damp, except damp and hot;Modern chemistry and pharmacology Learn research shows that:Radix scutellariae is to shigella dysenteriae, typhoid bacillus, comma bacillus, Escherichia coli, proteus, Pseudomonas aeruginosa, grape ball Bacterium, hemolytic vessel used to hold grain at the imperial sacrifice coccus (a, B) etc. have inhibiting effect.
Meanwhile helped in composition provided by the invention with Folium Loropetali, Vitex negundo var cannabifolia, elephants-foot, iron holly bark, cloves etc., Have the function of good antibacterial, improve immunity of organisms;Clearing heat and detoxicating, righting of getting rid of evils the work(of the existing Chinese medicine of the prescription compatibility of medicines, There is the antibacterial of modern medicine again, desinsection, adjust the benefits of immune function, have effects that maintain intestinal health, is that treatment drug resistance is thin The good recipe of bacterium infectious diseases has the function of good overriding resistance bacterial infection disease.
In some embodiments of the invention, can also include 200-700 parts by weight of auxiliary material in the composition.It can be with Understanding, the main function of auxiliary material is figuration, dilution and anti-corrosion etc., and the present invention is not particularly limited the type of auxiliary material, It can be various common auxiliary materials, for example, in some embodiments of the invention, the auxiliary material is in dextrin, glucose It is one or more.
Meanwhile the present invention also provides a kind of preparation methods for treating drug-resistant bacteria disease composition comprising following steps:
S1, the mixture 2 times that half of lotus flower and radix scutellariae are extracted with ethanol solution, it is 1-2 hour each, merge after filtering and filters Liquid, and be concentrated under reduced pressure into thick paste A at 60-80 DEG C, wherein a concentration of the 75% of extraction ethanol solution used every time, every time The weight of extraction ethanol solution used is 10-20 times of the total weight of the mixture of the half of lotus flower and radix scutellariae;
S2, with ethanol solution extraction X 2 times, 1-2 hours each, merging filtrate after filtering, and depressurizing at 60-80 DEG C dense Shorten thick paste B into, wherein extract a concentration of the 50% of ethanol solution used for the first time, second of extraction ethanol solution used A concentration of 30%, 8-12 times of the weight that the weight of extraction ethanol solution used is X every time, the X for selected from Folium Loropetali, It is one or more in Vitex negundo var cannabifolia, elephants-foot, iron holly bark, cloves;
S3, the thick paste A is merged with the thick paste B, obtains thick paste C;And
S4, by the thick paste C and auxiliaries at the treatment drug-resistant bacteria disease composition.
It is understood that the operating method and principle that are extracted with ethanol solution by those skilled in the art public affairs Know, the present invention repeats no more this.
In the preparation method for the treatment of drug-resistant bacteria disease composition provided by the invention, the X is selected from Folium Loropetali, Vitex negundo var cannabifolia It is one or more in flower, elephants-foot, iron holly bark, cloves.It is understood that in step S2) in, X can there are many choosings It selects, can be one kind in Folium Loropetali, Vitex negundo var cannabifolia, elephants-foot, iron holly bark or cloves, or Folium Loropetali, Vitex negundo var cannabifolia Two or more in flower, elephants-foot, iron holly bark or cloves.Likewise, when X is Folium Loropetali, Vitex negundo var cannabifolia, elephants-foot, rescues Must answer or cloves in two or more when, X can be extracted respectively, filter and merge thick paste after concentrating, obtain thick paste B can also be that X is carried out ethyl alcohol extraction together, be filtered and concentrated to thick paste B.
It is understood that the concrete operation method and principle that are concentrated under reduced pressure are known to those skilled in the art, this hair Bright no longer to be repeated this, reduced pressure method commonly used in the art may be used in the present invention.
Further, in some embodiments of the invention, step S4 includes that the thick paste C is added in the auxiliary material, is stirred Wet granular is made through granulator after even, then dry at 60-80 DEG C, whole grain, packing, sealing, with the drug-resistant bacteria that obtains medical treatment Sick composition granule.It is understood that the preparation method of wet granular, whole grain, packing and the method for sealing are this field skill Known described in art personnel, the present invention no longer repeats this.
Further, in some embodiments of the invention, the step S1) described in the weight of thick paste A be described half The 1/3-2/3 of the total weight of the mixture of side lotus flower and radix scutellariae, such as 1/2.The step S2) described in the weight of thick paste B be The 1/4-1/2 of the total weight of the X, such as 1/3.The step S3) described in the weight of thick paste C be the half of lotus flower, institute State the 1/4-3/4 of the total weight of radix scutellariae and the X, such as 1/3.
In addition, the answering in preparing the drug for treating drug-resistant bacteria disease the present invention also provides a kind of above-mentioned composition With.
Specifically, in some embodiments of the invention, the drug-resistant bacteria in the drug-resistant bacteria disease is drug resistance intestines bar Bacterium, Klebsiella Pneumoniae, staphylococcus aureus, Salmonella, enterococcus faecium and Shiga bacillus etc. and tuberculosis bar Bacterium, comma bacillus, vibrio parahemolyticus or Vibrio vulnificus.
The invention is further illustrated by the following examples, but the embodiment is merely to illustrate the present invention rather than limits The present invention.
Embodiment 1
It is a kind of to treat drug-resistant bacteria disease composition, be by half of lotus flower, radix scutellariae, Folium Loropetali, iron holly bark, cloves, dextrin, The medicament that glucose is prepared by following weights:
The preparation process of the treatment drug-resistant bacteria disease composition of the present embodiment described further below:
(1) together by half of lotus flower, radix scutellariae, it is extracted 2 times with 10 times of 75% ethyl alcohol of amount, 1 hour every time, filter is merged after filtration Liquid recycles ethyl alcohol, and at 75 DEG C, at thick paste A, (wherein, the weight ratio between medicinal material and thick paste A is 2 for reduced pressure:1).
(2) by Folium Loropetali, iron holly bark, cloves respectively with 8 times amount 50% ethyl alcohol, 30% ethyl alcohol extract 2 times, 1 hour every time, Ethyl alcohol is recovered under reduced pressure at 75 DEG C, is condensed into thick paste B for merging filtrate after filtration.
(3) merge thick paste A and thick paste B, obtaining thick paste C, (wherein, the total weight of medicinal material and the weight ratio of thick paste C are 3:1), It is spare.
(4) softwood processed:Thick paste C is added in glucose and dextrin, stirs evenly to obtain softwood.
(5) it pelletizes:Wet granular is made through granulator in the softwood, then dry at 75 DEG C, whole grain, packing, sealing, Obtain medical treatment drug-resistant bacteria disease composition granule.
Embodiment 2
It is a kind of to treat drug-resistant bacteria disease composition, be by half of lotus flower, radix scutellariae, Folium Loropetali, Vitex negundo var cannabifolia, elephants-foot, The medicament that dextrin, glucose are prepared by following weights:
The preparation process of the treatment drug-resistant bacteria disease composition of the present embodiment described further below:
(1) together by half of lotus flower, radix scutellariae, it is extracted 2 times with 10 times of 75% ethyl alcohol of amount, 1 hour every time, filter is merged after filtration Liquid recycles ethyl alcohol, and at 75 DEG C, at thick paste A, (wherein, the weight ratio between medicinal material and thick paste A is 2 for reduced pressure:1);
(2) by Folium Loropetali, Vitex negundo var cannabifolia and elephants-foot respectively with 8 times of 50% ethyl alcohol of amount, the extraction of 30% ethyl alcohol 2 times, every time 1 hour, ethyl alcohol was recovered under reduced pressure at 75 lower DEG C, is condensed into thick paste B for merging filtrate after filtration;
(3) merge A and thick paste B, obtaining thick paste C, (wherein, the total weight of medicinal material and the weight ratio of thick paste C are 3:1), standby With.
(4) softwood processed and the technique of (5) granulation are the same as embodiment 1.
Antibacterial experiment in vitro
1) minimum inhibitory concentration (Minimum Inhibitory Concentration, MIC) is tested
Composition provided by the invention is configured to multiple sample liquid with two times of gradient dilutions, is separately added into equivalent golden yellow Staphylococcus;Escherichia coli, comma bacillus, shigella dysenteriae, lapactic E.coli, vibrio parahaemolytious, detection of Salmonella, Fu Shi dysentery In Shigella, enterobacter cloacae, Vibrio vulnificus bacterium solution, sealing cultivates 24 hours at 28 DEG C, visually observes the minimum nothing of culture Bacterial growth person, as MIC (mg/ml) value of the composition.
MIC (mg/ml) value of composition in each bacterium solution is recorded after the test, wherein staphylococcus aureus, large intestine bar Bacterium, comma bacillus, shigella dysenteriae, lapactic E.coli, vibrio parahaemolytious, detection of Salmonella, Fu Shi shigella dysenteriaes, cloaca intestines Bacillus, Vibrio vulnificus MIC (mg/ml) value difference 0.78,3.13,0.29,6.25,12.50,0.78,12.50,12.50, 1.56 0.78.
2) suppression methicillin-resistant staphylococcus aureus (MRSA) is tested in vitro
The death rate of MRSA infection is high, it has also become the serious infections of global concern.Nearly all MRSA is to existing The antibiotic such as beta-lactam, cephalosporins, macrolides, quinolione class it is insensitive, the glycopeptides class such as vancomycin Antibiotic becomes the last line of defense for the treatment of MRSA infection, once drug resistance of vancomycin becomes universal phenomenon, clinic will face Without the available serious situation of medicine.
According to U.S. clinical Laboratory Standard association (Clinical and Laboratory Standards Institute, CLSI) regulation, using oxacillin antibiotic as standard, using K-B paper disk methods measurement inhibition zone diameter, inhibition zone ≤ 11mm is drug resistance, and >=17mm is sensitivity;Using broth dilution method determination minimum inhibitory concentration, MIC<2 μ g/ml are sensitivity,>4μ G/ml is drug resistance.
MIC experimental methods are:Composition provided by the invention is prepared sample liquid with two times of gradient dilutions, is separately added into Staphylococcus aureus and MRSA are measured, sealing, 28 DEG C are cultivated 24 hours, visually observe the minimum no bacterial growth person of culture, i.e., For MIC (mg/ml) value of the extract.Experimental result is:Staphylococcus aureus, MRSA MIC (mg/ml) value difference 0.39,0.39.The result shows that the present composition is consistent staphylococcus aureus, fungistatic effect, i.e. the MRSA present invention Composition there is no drug resistance.
Antibacterial activity in vivo is tested
Give mouse peritoneal injection minimum lethal dose (MLD) concentration bacteria suspension to each group mouse (in addition to normal group) intraperitoneal injection It causes to infect, respectively composition group of the invention, coptis group, normal group and model group.According to dosage mouse is filled daily Stomach, continuous gavage 3d.After the 3rd day whole medicine group gastric infusion 1h, with each strain injection volume 0.5/20 obtained by trial test (ml/g), it is administered once again after 6h after infection.Continue to give survival mice gastric infusion daily after infection, until experiment terminates.
Observe and record appetite, activity condition and the change of illness state for observing animal after infecting according to requirement of experiment.When dead Dissection in time, visually observing body surface, whether there is or not the lesions such as oedema, bleeding and enlargement, abdominal cavities whether there is or not lesion, skin histology and lymph node Liquid is how many and property, thoracic organs and pleural fluid have it is unchanged.Animal dead situation in 3 days after statistics infection, records dead example Number and death time put to death all animals on the 5th day, and entire experimental period is 5 days.
The common clinical symptom of mouse appearance is after infection:Primary stage of inoculation, all there is lassitude in mouse, dispirited, eye knot The symptoms such as film coalescence, activity are reduced, and feeding, drinking-water are reduced.
In comparison, the appetite Yu activity condition of each administration group mouse are better than model group.Later stage disease mouse extremely weak, eye For cheesy closing, until dead.The major lesions of each group mouse tissue organ include the abscess of inoculation position, peritonaeum after dissection Chamber mucus, foul smelling, lungs extravasated blood etc..
Before putting to death all animals, each group protective rate (death rate=every group of animal number of every group of dead animal number ÷ is calculated × 100%);The death time of 3 days (72h) interior each group mouse after record infection, the credit that takes statistics analysis.
Experimental result is:In terms of the death rate and time-to-live:(1) normal group, each medicine group are compared with model group, difference Statistically significant (P<0.01).(2) composition that the present invention improves is to staphylococcus aureus, Escherichia coli, Fu Shi dysentery Disease shigella infection mouse protective effect best results.(3) compared with positive controls, in terms of the death rate, life span, Significant effect is better than the coptis.
Inhibiting effect research in animal body to MRSA
All there is lassitude in primary stage of inoculation mouse, dispirited, eye conjunctiva adhesion, and activity is reduced, and feeding, drinking-water are reduced.Phase Than for, appetite and the activity condition of each administration group mouse are better than model group.Later stage disease mouse is extremely weak, and eye is cheesy envelope It closes, until dead.The major lesions of each group mouse tissue organ include the abscess of inoculation position, cavum peritoneale mucus, have after dissection Stench, lungs extravasated blood etc..
Before putting to death all animals, each group protective rate (death rate=every group of animal number of every group of dead animal number ÷ is calculated × 100%) death time of 3 days (72h) interior each group mouse after, record infects, the credit that takes statistics analysis:Death rate ratio between each group Compared with using Chi-square Test, the time-to-live compares using paired t-test.
Experiment measures protective effect of the drug to MRSA infection model mouse, in terms of the death rate and time-to-live:(1) just Normal group, each medicine group are compared with model group, the statistically significant (P of difference<0.01).(2) composition of the invention and the positive Control group is compared, and in terms of the death rate, life span, effect is better than the coptis.
As a result it proves:Composition provided by the invention can significantly reduce the death rate of MRSA infection model mouse, and can show It writes and extends the time-to-live.
Antibacterial activity in vivo test and animal body in the inhibiting effect research of MRSA the result shows that, in vivo to this hair Bright composition 8.0g/Kg dosage, animal body is interior to play obviously staphylococcus aureus and MRSA infection models mouse Protective effect, can significantly reduce the death rate and extend the time-to-live.That is the MRSA present compositions do not have drug resistance.
Acute toxicity testing
Using healthy Kunming mouse as experimental animal, before testing after fasting (can't help water) 12h, it is (raw that 1.2g is given respectively Medicine)/mL (maximum concentration) the present composition, be administered once per 4h, be administered three times a day;It is observed continuously one week, records tested Mouse has Non Apparent Abnormality and time, Symptoms and the duration of toxic reaction occurs;Dead example is seen whether, in time It is substantially become celestial, whether there is or not apparent pathological changes for observation internal organs;The weight of animals is weighed daily;All experiments are put to death after the test Animal, and become celestial.The day maximum dosage-feeding for calculating each test medicine, evaluates its safety.
It has no dead in experimentation, can not measure LD50, therefore according to《Chinese medicine, natural drug studies on acute toxicity technology Guideline》The experiment that regulation carries out maximum dosage-feeding measures.Gavage is to present composition integral dose in mouse 1 day 108g/Kg (maximum dosage-feeding=1.2g (crude drug)/ml × 0.3ml × 3/10g × 100=108g (crude drug)/Kg), experiment are not seen Overt toxicity reaction is observed, it is higher that safety is administered orally in preliminary proof mouse at this dose.
Although an embodiment of the present invention has been shown and described, it will be understood by those skilled in the art that:Not In the case of being detached from the principle of the present invention and objective a variety of change, modification, replacement and modification can be carried out to these embodiments, this The range of invention is limited by claim and its equivalent.

Claims (7)

1. a kind for the treatment of drug-resistant bacteria disease composition, which is characterized in that include following components of following weight parts:Half of lotus flower 200-400 parts by weight, 100-300 parts by weight of radix scutellariae, 100-300 parts by weight of X, wherein X be Folium Loropetali, Vitex negundo var cannabifolia, courage It is one or more in the showy flowers of herbaceous plants, iron holly bark, cloves.
2. composition according to claim 1, which is characterized in that the composition also includes 200-700 weight of auxiliary material Part, the auxiliary material is one or more in dextrin, glucose.
3. a kind of preparation method for treating drug-resistant bacteria disease composition, which is characterized in that include the following steps:
S1, the mixture 2 times that half of lotus flower and radix scutellariae are extracted with ethanol solution, 1-2 hours each, merging filtrate after filtering, and It is concentrated under reduced pressure into thick paste A at 60-80 DEG C, wherein a concentration of the 75% of extraction ethanol solution used every time extracts institute every time The weight of ethanol solution is 10-20 times of the total weight of the mixture of the half of lotus flower and radix scutellariae;
S2, with ethanol solution extraction X 2 times, 1-2 hour each, merging filtrate after filtering, and at 60-80 DEG C reduced pressure at Thick paste B, wherein extract a concentration of the 50% of ethanol solution used for the first time, extract the dense of ethanol solution used for the second time Degree is 30%, and 8-12 times of the weight that the weight of extraction ethanol solution used is X every time, the X is selected from Folium Loropetali, Vitex negundo var cannabifolia It is one or more in flower, elephants-foot, iron holly bark, cloves;
S3, the thick paste A is merged with the thick paste B, obtains thick paste C;And
S4, by the thick paste C and auxiliaries at the treatment drug-resistant bacteria disease composition.
4. preparation method according to claim 3, which is characterized in that step S4 includes that the thick paste is added in the auxiliary material Wet granular is made through granulator after stirring evenly in C, then dry at 60-80 DEG C, whole grain, packing, sealing, with the drug resistance that obtains medical treatment Bacterial disease composition granule.
5. preparation method according to claim 3, which is characterized in that the step S1) described in the weight of thick paste A be institute State the 1/3-2/3 of the total weight of the mixture of half of lotus flower and radix scutellariae;The step S2) described in thick paste B weight be the X Total weight 1/4-1/2;The step S3) described in the weight of thick paste C be the half of lotus flower, the radix scutellariae and described The 1/4-3/4 of the total weight of X.
6. application of the claim 1-2 any one of them composition in preparing the drug for treating drug-resistant bacteria disease.
7. application according to claim 6, the drug-resistant bacteria in the drug-resistant bacteria disease is drug resistance enterobacteria, pneumonia gram The primary bacterium of thunder, staphylococcus aureus, Salmonella, enterococcus faecium, Shiga bacillus, tubercle bacillus, comma bacillus, secondary haemolysis Property vibrios or Vibrio vulnificus.
CN201810555304.2A 2018-06-01 2018-06-01 It is a kind of to treat drug-resistant bacteria disease composition and its preparation method and application Pending CN108403766A (en)

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