CN111529572B - A Scutellariae radix extract self-microemulsion with biological antibacterial effect - Google Patents
A Scutellariae radix extract self-microemulsion with biological antibacterial effect Download PDFInfo
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- 239000004530 micro-emulsion Substances 0.000 title claims abstract description 68
- 239000000284 extract Substances 0.000 title claims abstract description 57
- 230000000844 anti-bacterial effect Effects 0.000 title description 19
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/539—Scutellaria (skullcap)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A61P31/04—Antibacterial agents
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- A61K2236/30—Extraction of the material
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
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Abstract
The invention discloses a self-microemulsion of radix scutellariae extract with biological bacteriostasis, which is prepared from 2-6% of radix scutellariae CO 2 The supercritical extract is active substance, and is mixed with 10-40% of nonionic surfactant, 20-50% of short-chain fatty alcohol and 20-55% of modified vegetable oil to form self-microemulsion which is easy to form a thermodynamically stable microemulsion system with water. The self-microemulsion of the invention can be used as livestock and poultry sterilizing bacteriostat and livestock and poultry growth promoter after being diluted by water, and is used for promoting the growth of livestock and poultry and improving the immunity.
Description
Technical Field
The invention belongs to the technical field of veterinary medicines, and relates to a self-microemulsion with biological antibacterial performance based on active substance components of scutellaria baicalensis extract.
Background
The long-term use of antibiotics has led to the emergence of widely resistant pathogens. Development of a novel antibacterial agent with high safety and high antibacterial activity and difficult generation of drug resistance is a problem to be solved in the current livestock and poultry breeding process.
The Chinese herbal medicine has small toxic and side effects, no residue, difficult drug resistance generation, medicinal and nutritional effects, and has been applied to livestock and poultry cultivation.
Radix ScutellariaeScutellaria baicalensisGeorgi) is derived from dry root of Scutellaria baicalensis Georgi belonging to Labiatae, and has antibacterial, liver protecting, antiviral, antioxidant, free radical scavenging, antiallergic, and neuron protecting effects. The baicalin, the wogonin and the baicalin extracted from the baicalin, the wogonin have antibacterial and antibacterial effects and the immunity of livestock is enhanced. A large number of researches show that baicalein and wogonin are substances in the radix scutellariae which truly play a role in medicine, and baicalin and wogonin also need to be hydrolyzed into aglycone baicalein and wogonin through intestinal flora to play a role.
However, baicalein and wogonin are fat-soluble compounds with strong hydrophobicity, common medicinal solvents such as polyalcohol, water and the like can not effectively dissolve the baicalein and wogonin, so that a good antibacterial and bacteriostatic effect can not be achieved, and the baicalein and wogonin can not be added into drinking water for promoting healthy growth of livestock and poultry. The direct use of baicalein and wogonin has the problems of easy oxidation and inactivation, poor solubility in water, incapability of being effectively dispersed and the like, thereby affecting the efficacy of the medicine.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the self-microemulsion of the scutellaria baicalensis extract with biological bacteriostasis, which is easy to form a thermodynamically stable microemulsion system with water.
The self-microemulsion of the baical skullcap root extract is prepared by using baical skullcap root CO 2 The supercritical extract is an active substance, and is mixed with nonionic surfactant, short-chain fatty alcohol and modified vegetable oil to form the self-microemulsion with biological antibacterial property.
Specifically, the self-microemulsion is prepared from nonionic surfactant, modified vegetable oil, short-chain fatty alcohol and baical skullcap root CO 2 The supercritical extract is prepared by mixing the following components in percentage by mass: 10-40% of nonionic surfactant, 20-55% of modified vegetable oil, 20-50% of short-chain fatty alcohol and 20-50% of baical skullcap root CO 2 2-6% of supercritical extract.
The invention uses the nonionic surfactant, short-chain fatty alcohol, modified vegetable oil and baical skullcap root CO 2 The reasonable combination of the supercritical extracts forms the self-microemulsion with biological antibacterial performance. Diluting the self-microemulsion with water, and collecting Scutellariae radix CO 2 The supercritical extract will be present in the diluent in a dispersed state of less than 100nm. When diluted by water, the self-microemulsion can form a thermodynamically stable microemulsion system with water, and the diluent is clear and transparent in appearance, does not delaminate and has no sediment.
Wherein the baical skullcap root CO 2 Supercritical extracts are prepared using conventional CO 2 The material obtained by extracting radix Scutellariae by supercritical extraction method comprises baicalein and wogonin as main ingredients.
Specifically, the nonionic surfactant in the self-microemulsion is a mixture composed of span-80 and tween-60 and/or tween-20.
More specifically, the modified vegetable oil is polyoxyethylene castor oil, and isopropyl laurate and/or isopropyl myristate are added to the modified vegetable oil.
Further, the short-chain fatty alcohol is one or more of isopropanol, glycerol and ethylene glycol.
The self-microemulsion with biological bacteriostasis can be prepared according to the following method: nonionic surfactant, modified vegetable oil, short chain fatty alcohol and Scutellariae radix CO 2 And (3) putting the supercritical extract into a stirring kettle according to the mass percentage, stirring and mixing until the supercritical extract is in a transparent and uniform state, and preparing the self-microemulsion.
The self-microemulsion with biological bacteriostasis prepared by the invention is diluted by water and can be used after being uniformly stirred. The particle size of the dispersed phase liquid drops of the self-microemulsion diluted by water is smaller than 100nm.
The self-microemulsion can be used as a livestock and poultry sterilizing bacteriostat. When used for bacteriostasis, the water is added according to the mass ratio and diluted by 50-100 times for use.
The self-microemulsion with biological bacteriostasis can also be used as a livestock and poultry growth promoter for promoting the growth of livestock and poultry and improving the immunity. When being used as the livestock and poultry growth promoter, the water is added according to the mass ratio to dilute the livestock and poultry growth promoter by 100-500 times.
The invention adopts self-microemulsion technology to prepare the self-microemulsion of the baical skullcap root extract, so that the baical skullcap root CO 2 The supercritical extract can be dispersed in water in a state smaller than 100nm after being diluted with water to form a thermodynamically stable system with uniform and transparent appearance, no layering or precipitation, and no precipitation, thereby solving the problem of radix Scutellariae CO 2 The supercritical extract is difficult to be directly used, and the drug effect is obviously improved.
The bacteriostasis evaluation test aiming at escherichia coli shows that the minimum bacteriostasis concentration of the self-microemulsion is only 1/53 of the concentration of the traditional baicalin water extract (main components of baicalin and wogonin). The antibacterial evaluation test on staphylococcus aureus also shows that the minimum antibacterial concentration of the self-microemulsion is only 1/16 of the concentration of the traditional radix scutellariae water extract.
Compared with blank groups, the self-microemulsion can improve the average weight of 42-day-old broilers by more than 10%, and the thymus, spleen and bursa indexes are respectively improved by more than 5%, 30% and 11%, so that the systemic immune level of animals is remarkably improved.
Drawings
FIG. 1 is the effect of Scutellariae radix extract from microemulsion on E.coli growth curve.
FIG. 2 is the effect of aqueous extract of Scutellaria baicalensis on the growth curve of E.coli.
FIG. 3 is the effect of Scutellariae radix extract from microemulsion on Staphylococcus aureus growth curve.
FIG. 4 is the effect of aqueous extract of Scutellariae radix on Staphylococcus aureus growth curve.
Detailed Description
The following describes the invention in further detail with reference to examples. The following examples are only for more clearly illustrating the technical aspects of the present invention, and are not intended to limit the scope of the present invention. Various changes, modifications, substitutions and alterations may be made by those skilled in the art without departing from the principles and spirit of the invention, and it is intended that the invention encompass all such changes, modifications and alterations as fall within the scope of the invention.
Example 1.
Adding 10g span-80, 4g Tween-20 into 50g polyoxyethylene castor oil, stirring, mixing, adding 30g isopropanol, stirring, mixing, adding 6g Scutellariae radix CO 2 The supercritical extract is stirred and mixed until the appearance is clear and transparent, and the self-microemulsion with biological bacteriostasis is prepared.
Example 2.
Adding 10g isopropyl laurate, 15g isopropyl myristate, stirring, mixing, adding 6g span-80, 2g Tween-20, 2g Tween-60, stirring, mixing, adding 20g isopropanol, 10g glycerol, stirring, mixing, and adding 5g Scutellariae radix CO 2 The supercritical extract is stirred and mixed until the appearance is clear and transparent, and the self-microemulsion with biological bacteriostasis is prepared.
Example 3.
Adding 14g isopropyl laurate into 14g polyoxyethylene castor oil, stirring, mixing, adding 6g span-80, 14g tween-60, stirring, mixing, adding 20g isopropanol, 20g glycerol, 10g ethylene glycol, stirring, mixing, adding 2g Scutellariae radix CO 2 The supercritical extract is stirred and mixed until the appearance is clear and transparent, and the self-microemulsion with biological bacteriostasis is prepared.
Example 4.
Adding 22g isopropyl myristate into 15g polyoxyethylene castor oil, stirring and mixing uniformly, adding 15g span-80, 15g tween-20 and 10g tween-60, stirring and mixing uniformly, adding 20g glycerol, stirring and mixing uniformly, adding 3g radix Scutellariae CO 2 The supercritical extract is stirred and mixed until the appearance is clear and transparent, and the self-microemulsion with biological bacteriostasis is prepared.
Example 5.
Adding 10g isopropyl myristate into 10g polyoxyethylene castor oil, stirring and mixing uniformly, adding 14g span-80, 12g tween-20 and 12g tween-60, stirring and mixing uniformly, adding 20g glycerol and 20g glycol, stirring and mixing uniformly, adding 3g Scutellariae radix CO 2 The supercritical extract is stirred and mixed until the appearance is clear and transparent, and the self-microemulsion with biological bacteriostasis is prepared.
Example 6.
Adding 10g isopropyl myristate into 10g polyoxyethylene castor oil, stirring, mixing, adding 14g span-80, 12g tween-20, 12g tween-60, stirring, mixing, adding 40g glycol, stirring, mixing, adding 3g Scutellariae radix CO 2 The supercritical extract is stirred and mixed until the appearance is clear and transparent, and the self-microemulsion with biological bacteriostasis is prepared.
Example 7.
Adding 26g isopropyl laurate into 20g polyoxyethylene castor oil, stirring, mixing, adding 10g span-80, 12g tween-20, stirring, mixing, adding 20g isopropanol, 10g glycol, stirring, mixing, adding 2g Scutellariae radix CO 2 The supercritical extract is stirred and mixed until the appearance is clear and transparent, and the self-microemulsion with biological bacteriostasis is prepared.
Application example 1.
The scutellaria baicalensis extracts prepared in examples 1 to 7 above were diluted 50-fold and 500-fold with water from the microemulsion, respectively, and the average particle size of the diluted solution was measured by a dynamic light scattering method using a Nano ZS dynamic light scattering instrument from Malvern company, and the detection results are shown in table 1.
As can be seen from Table 1, the particle size of each of the self-microemulsions after dilution with water was 100nm or less, and the particle size of the self-microemulsions was within the range of particle size of the microemulsions (10 to 100 nm), indicating that the microemulsions after dilution were uniformly dispersed and the appearance was similar to that of transparent or micro-transparent solutions.
Application example 2.
The diameter of the antibacterial circle of the baikal skullcap root extract prepared in examples 1-7 on the escherichia coli and staphylococcus aureus is measured by a filter paper sheet method, and the antibacterial activity of the baikal skullcap root extract from the microemulsion is examined.
Preparation of a solid culture medium: 1.0g of peptone, 0.5g of beef extract, 0.5g of sodium chloride and about 2.0g of agar powder are weighed, water is added for heating and dissolving, the volume is fixed to 100mL, 10% NaOH solution is used for adjusting the pH value to be 7.2-7.4, filtering and split charging are carried out, the mixture is placed in a triangular flask, and the triangular flask is placed in a 120Pa high-pressure steam kettle for 20min for standby after sterilization.
Preparing a liquid culture medium: except that no agar powder is added, other preparation methods are the same as those of the solid culture medium.
Activating strains: inoculating the strain on a slant culture medium on a sterile operation table, placing the strain in an incubator, and performing slant culture at 37 ℃ for 18-24 hours.
Preparing a bacterial suspension: selecting typical bacterial colony after activating and culturing, inoculating to sterilized liquid culture medium, culturing in 37 deg.C incubator for 24 hr, diluting to 10 with sterile physiological saline 6 CFU/mL was ready for use.
Pouring the sterilized solid culture medium into a culture dish subjected to dry heat sterilization in a sterile environment, wherein the thickness of the culture medium is not more than 2/3 of that of the culture dish, respectively sucking 200 mu L of escherichia coli and staphylococcus aureus bacterial suspension onto the culture medium by a pipette after the culture medium is solidified, marking, and uniformly coating by a coating rod.
The sterilized filter paper sheets are respectively put into the scutellaria baicalensis extracts prepared in examples 1 to 7 to be soaked in the microemulsion for 20min, and the filter paper sheets permeated with the microemulsion are taken out and closely attached to a solid culture medium. And blank self-microemulsions were used as controls.
The culture medium is placed in a 37 ℃ incubator to be cultured for 24 hours, the antibacterial effect is observed, the diameter of the antibacterial ring is measured, and each sample is repeated for 3 times. The measurement results are shown in Table 2.
As can be seen from Table 2, the Scutellariae radix extracts prepared in examples 1-7 have good antibacterial effect on Escherichia coli and Staphylococcus aureus from the microemulsion. Radix Scutellariae CO 2 The higher the concentration of the supercritical extract, the larger the diameter of the inhibition zone and the stronger the inhibition force.
Application example 3.
The water extract of the baical skullcap root is prepared according to the conventional method: reflux-extracting Scutellariae radix powder with water at a feed-liquid ratio of 1:10 for 3 hr, filtering, concentrating the filtrate under reduced pressure, and drying to obtain brown Scutellariae radix water extract.
The minimum inhibitory concentration performance was determined from the microemulsion using the above aqueous extract of scutellaria baicalensis and the extract of scutellaria baicalensis of example 1, respectively.
Coli and staphylococcus aureus are used as test bacteria, and bacterial suspension is prepared.
Preparing liquid culture medium corresponding to the strain of the test bacteria, respectively loading 100mL into 3 conical flasks of 250mL, marking as 1, 2, 3, autoclaving at 121deg.C for 20min, cooling, inoculating into 1mL of medium with proper concentration (10 5 CFU/mL).
Adding appropriate amount of Scutellariae radix extract self-microemulsion or Scutellariae radix aqueous extract solution into conical flask 1 and 2 respectively to reach final concentration of 1×MIC and 1/2×MIC, and taking normal strain 3 as control.
The Erlenmeyer flask was placed at 37℃and shake-incubated at 150r/min for 24h, during which time samples were taken every 2h under sterile conditions, absorbance OD values were measured and recorded at 600nm, and repeated 3 times. And drawing a growth curve of the test bacteria by taking time as an abscissa and an OD average value as an ordinate, wherein the specific growth curve results are shown in figures 1-4.
As can be seen from FIGS. 1-4, the Scutellariae radix extract has strong inhibiting effect on Escherichia coli and Staphylococcus aureus from the microemulsion, and has MIC value of 0.375mg/mL for Escherichia coli and 0.187mg/mL for Staphylococcus aureus. And the MIC value of the aqueous extract of scutellaria baicalensis to escherichia coli and staphylococcus aureus is only 20mg/mL and 3mg/mL respectively.
Therefore, the inhibition effect and the antibacterial effect of the radix scutellariae extract from the microemulsion on escherichia coli and staphylococcus aureus are obviously stronger than those of the radix scutellariae aqueous extract. The minimum antibacterial concentration of the bacillus coli is only 1/53 of the concentration of the traditional water extract of the scutellaria baicalensis (the main components of the baicalin and the wogonin); the minimum inhibitory concentration of staphylococcus aureus is only 1/16 of the concentration of the traditional radix scutellariae water extract.
Application example 4.
Taking white feather broilers as experimental objects, examining the results of growth experiments and whole body immunity evaluation after feeding the broiler feed water with a small amount of the scutellaria baicalensis extracts prepared in examples 1-4.
White feather broilers 350 feathers, which are healthy at 1 day old and close in weight, were selected and randomly divided into a blank group, 4 baical skullcap root extracts from the microemulsion experimental group (experimental group 1, experimental group 2, experimental group 3, experimental group 4), and baical skullcap root extracts from the microemulsion control group (control group 1) and the baical skullcap root aqueous extract control group (control group 2) 7 groups, each group being repeated 50 times.
The blank group is normally fed with basic ration without antibiotics and is given with tap water for drinking.
The 4 radix Scutellariae extracts were diluted 200 times from the microemulsion respectively on the basis of normal feeding without antibiotic base ration, and were fed with drinking water.
The Scutellariae radix extract is prepared from microemulsion control group according to the content of Scutellariae radix CO 2 The extract of Scutellaria baicalensis Georgi of example 1 was fed by adding the extract of Scutellaria baicalensis Georgi to the basic ration without antibiotics at a dosage of 0.03%, and drinking water was given.
The radix scutellariae water extract control group is fed with water with the content of 0.03% of radix scutellariae water extract on the basis of normal feeding without antibiotic basic ration.
The raising period is 42 days. After feeding, the effect of the different feeding modes of the baikal skullcap root extract from the microemulsion and the effect of the baikal skullcap root aqueous extract on the growth and immune organ index of white feather broilers are evaluated by comparison with a blank group, and the specific comparison results are shown in table 3.
Weight gain = (average weight of experimental group or control group-average weight of blank group)/(average weight of blank group) ×100%.
Thymus, spleen and bursa index increase rate = (average index of experimental or control group-average index of blank)/(average index of blank) ×100%.
The results in table 3 show that, compared with the blank group, the average weight of 42-day-old broilers can be improved by more than 10% and the maximum improvement is approximately 20% by adding the self-microemulsion of the invention into drinking water for feeding; the thymus index, the spleen index and the bursa index of 42-day-old broiler chickens are respectively improved by more than 5%, 30% and 11%, and the systemic immunity level of animals is obviously improved.
The same self-microemulsion is mixed in the basic ration for direct feeding, and the weight and immune organ index of the broiler chicken can be improved, but compared with the drinking water adding mode with the same concentration, the effect is obviously deteriorated, and the feeding mode that the self-microemulsion is mixed in the basic ration is shown that the bioavailability of the broiler chicken to the medicine is not as good as that of the drinking water mode.
Meanwhile, the weight and immune organ index of the broiler chickens are basically the same as those of the blank groups when the baical skullcap root aqueous extract is added into drinking water for feeding, which shows that the bioavailability of the baical skullcap root aqueous extract is lower and the difference is obvious compared with the self-microemulsion with the same concentration.
Average daily gain of livestock and poultry is an important index for reflecting the effectiveness of the additive. The experimental result shows that the average daily gain of the broiler chicken can be obviously improved and the economic benefit of raising the chicken can be greatly improved by adding a small amount of the baical skullcap root extract self-microemulsion into the broiler chicken feeding water.
The development status and the function intensity of animal immune organs directly determine the whole body immune level of poultry, namely the quality of immune organs can be used for evaluating the immune state of chickens. The Scutellaria baicalensis extract self-microemulsion can improve thymus, spleen and bursa index of broiler chickens, and greatly improve the systemic immune level of animals. The baicalin extracted from the microemulsion is dispersed in a nano-scale way, so that the medicine is easy to be absorbed in vivo, and the bioavailability of baicalin extracted from the microemulsion is verified to be much higher than that of baicalin.
Claims (2)
1. The application of the baical skullcap root extract self-microemulsion in preparing the livestock and poultry growth promoter is characterized in that the preparation process of the baical skullcap root extract self-microemulsion is as follows:
adding 14g isopropyl laurate into 14g polyoxyethylene castor oil, stirring, mixing, adding 6g span-80, 14g tween-60, stirring, mixing, adding 20g isopropanol, 20g glycerol, 10g ethylene glycol, stirring, mixing, adding 2g Scutellariae radix CO 2 The supercritical extract is stirred and mixed until the appearance is clear and transparent, and the self-microemulsion with biological bacteriostasis is prepared;
the baical skullcap root CO 2 Supercritical extracts are prepared using conventional CO 2 The material obtained by extracting radix Scutellariae by supercritical extraction method comprises baicalein and wogonin as main ingredients.
2. The use according to claim 1, wherein the scutellaria baicalensis extract is diluted 100 to 500 times by mass with water from the microemulsion.
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