CN100493600C - Pharmaceutical composition for preventing and curing endometritis and retained afterbirth disease of milk cow - Google Patents

Pharmaceutical composition for preventing and curing endometritis and retained afterbirth disease of milk cow Download PDF

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CN100493600C
CN100493600C CNB2005100191584A CN200510019158A CN100493600C CN 100493600 C CN100493600 C CN 100493600C CN B2005100191584 A CNB2005100191584 A CN B2005100191584A CN 200510019158 A CN200510019158 A CN 200510019158A CN 100493600 C CN100493600 C CN 100493600C
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carbomer
endometritis
oxytocin
stir
pharmaceutical composition
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CN1730097A (en
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杨利国
莫莉
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Huazhong Agricultural University
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Abstract

The invention discloses a combined medicinal composition for the prevention and treatment of cow's endometritis, the preparation process and use, wherein the medicinal composition comprises right amount of Povidone iodine, potassium iodate, propylene glycol or glycerin, oxytocin, estrogen, carbomer, sodium hydroxide and water.

Description

The pharmaceutical composition of a kind of prevention and treatment cow endometritis and retained afterbirth
Technical field
The invention belongs to technical field of animal remedy preparation, be specifically related to composition of medicine of a kind of prevention and treatment cow endometritis and retained afterbirth and its production and application, this medicine is mainly used in the prevention and the treatment of cow endometritis and retained afterbirth, to improve the breeding potential of milch cow.
Background technology
Cow endometritis is the comparatively common a kind of multiple disease of raising dairy cattle industry, generally falls ill more than 30%.Puerperal 2, all uterus were subjected to germ contamination very common.At the commitment in puerperal, have 93% milch cow nearly take place in various degree the intrauterine bacterial infection (Elliott, L., McMahon, K.J., Gier, H.T.and Marion, G.B.1968).Endometritis not only can cause the part milch cow long-term infertile or the cattle farm conception rate is on the low side, reduce milk production of cow, bring out diseases such as mastitis, cause consumer to raise, and the severe infection case also can cause the forfeiture of cow reproduction ability, thereby make the part milch cow be forced to eliminate, economic loss is serious.Cow endometritis mostly is antibacterial, virus, fungus, mycoplasma mixed infection and causes.The milch cow placenta retention also is a kind of very common disease, is meant that afterbirth fails in 8h~12h to discharge after normal labor.Studies show that placenta retention takes place the branch puerperium the milch cow probability that placenta retention takes place when producing of regenerating later on is bigger, and its metabolic disease, mastitis, metritis and that the sickness rate of miscarriage takes place later on is higher.
At present both at home and abroad to the treatment of cow endometritis still based on antibiotic therapy, field study shows, to endometritis suffer from cattle and the cattle uterus of oestrusing repeatedly in the various antibiotic of injection treat and can not really eliminate endometritis and can not improve reproductive capacity (Robert, S.J.. referring to " cow disease " Chinese translation, the China Agricultyre University Press, 2000).In utero antibiotic absorbs from the uterus easily, and is residual that antibiotic reaches detectable level in making blood and suckling, and causes the discarded of milk, causes enormous economic loss.And some antibiotic also can disturb cytophagous function, may stimulate endometrium, may be destroyed and inactivation by bacteriogenic beta-lactamase, (Miller perhaps can not well play a role under the relative anaerobic condition in uterus, H.V.. referring to " cow disease " Chinese translation, the China Agricultyre University Press, 2000).Intrauterine uses antibiotic biggest obstacle to be that a large amount of uterine hydrops can cover or reduce low dose of antibiotic effect.Use the intrauterine treatment in serious metritic case, many medicines are just as " a big marine water ".In addition, antibiotic long-term a large amount of bacterial drug resistances that caused of using can not be ignored.Produce effects not good and cause the waste of medicine by the way that increases using dosage or change the antibiotic kind, increased feeding and management one-tenth; It is slow to use the treatment by Chinese herbs drug action, so that state of an illness protracted course of disease or outbreak repeatedly, thereby clinical effectiveness is also not good.
To placenta retention treat attitude and method on, some veterinarys and the attitude that poultry is main takes " wait for and look around " avoid using antibiotic medicine as far as possible.Have data to show, puerperal undressed milch cow placenta retention sickness rate up to 17.7%, and equal secondary endometritis.Can cause a lot of dysfunctions of milch cow in case placenta retention takes place, and the risk bigger (Corhn, Y.T. is referring to " cow disease " Chinese translation, China Agricultyre University Press, 2000) of endometritis takes place later on.Tradition is to take to inject hormone to cooperate antibiotic use to the prevention and the treatment of placenta retention, the program of treatment is loaded down with trivial details and cause residues of antibiotics in the blood Ruzhong, verified, to the cattle of placenta retention puerperal early stage intrauterine use the 5g oxytetracycline every day, the residual quantity of milk Chinese medicine is raise the time more than 2 days, in other cases, the last time after the treatment, residually in the milk reach 4 days (" cow disease " Chinese translation, China Agricultyre University Press, 2000).
Povidone iodine is a kind of new and effective, wide-spectrum bactericide, is the conjugate of polyvinylpyrrolidone and iodine, and its available iodine content is 9%~12%.Polyvinylpyrrolidone is as the carrier of iodine, and penetrable bacterial membrane makes povidone iodine enter thalline, discharges the diatomic free-iodine, makes sulfohydrate in the cell, protein, material oxidation such as enzyme and VitC and instantaneous kill bacteria.Compare with iodine tincture or iodine solution, its feature is a no sensitization, almost non-stimulated to mucosa, does not cause the Drug resistance (Hu Zhaoyong bends peace, 1998) of antibacterial, virus.Povidone iodine has been made into the sterilizing that multiple dosage form is used for mucocutaneous grade aspect the people, and obviously (spray is referring to Chinese invention patent ZL 03131706.5 for curative effect; Membrane is referring to ZL 98111921.2 and patent of invention prospectus 03117635.6; Water preparation is referring to ZL 02104924.6; Ointment is referring to ZL 01127705.X; ), povidone iodine and composition of medicine thereof are used for the prevention and the treatment of cow endometritis and retained afterbirth and do not see document announcement as yet.
Solve prevention and the more existing relevant reports of treatment of cow endometritis at present, Chinese invention patent ublic specification of application for example, number of patent application is that 03142299.3 document discloses a kind of biological preparation of cow endometritis and preparation method thereof that is used to prevent and treat, said preparation comprises staphylococcus lysozyme, lysozyme, bacteriostatic peptide, protein stabilizing agent, penetration enhancer and medically acceptable carrier, utilize this biological preparation at the external bacteriostatic test that carries out related microorganism, still lack zooperal relevant data, the strain of mentioned production staphylococcus lysozyme comes from the engineering strain that oneself makes up, and this bacterial strain is used for the preservation of proprietary program as yet, therefore it is insufficient to cause its patent application to disclose, and those skilled in the art is difficult to carry out its invention according to present patent application text.
Summary of the invention
The objective of the invention is to overcome the defective of traditional therapy and prior art existence, a kind of convenient drug administration is provided, efficient, safety, the preparation of pharmaceutical compositions method and the application thereof of the prevention of noresidue and treatment cow endometritis and retained afterbirth are to improve the reproductive capacity of milch cow.
The present invention is achieved in that
The pharmaceutical composition of a kind of prevention and treatment cow endometritis and retained afterbirth, in parts by weight, its component is as follows:
0.2~10 part of povidone iodine
0.01~4 part of potassium iodate
1~30 part of propylene glycol or glycerol
0.05~1.5 part of oxytocin (having another name called oxytocin)
0.0~0.5 part of estrogen
0.1~5 part of carbomer
0.2~3 part of sodium hydroxide
Keep the skin wet to 100 parts;
It prepares in accordance with the following methods:
(1) carbomer is added little water and stir, fully swelling;
(2) sodium hydroxide is added in the carbomer of step (1), obtain gel-type vehicle;
(3) povidone iodine is joined in the gel-type vehicle that step (2) obtains, stir;
(4) with little water potassium iodate is made solution and will add in the lump behind oxytocin, estrogen and propylene glycol or the glycerol mixing in the product of step (3) gained;
(5) keep the skin wet to the full dose of above-mentioned prescription.
Preferred described pharmaceutical composition, in parts by weight, its component is as follows:
0.2~10 part of povidone iodine
0.01~4 part of potassium iodate
1~30 part of propylene glycol
0.05~1.5 part of oxytocin
0.0~0.5 part of estrogen
0.1~5 part of carbomer
0.2~3 part of sodium hydroxide
Keep the skin wet to 100 parts;
A kind of preparation of drug combination method that is used to prevent and treat cow endometritis and retained afterbirth, according to the following step:
(1) carbomer is added little water and stir, fully swelling;
(2) carbomer that sodium hydroxide is added step (1) obtains gel-type vehicle;
(3) stir adding povidone iodine in the gel-type vehicle of step (2), again potassium iodate is dissolved in little water, add in the lump behind oxytocin, estrogen and propylene glycol or the glycerol mixing;
(4) keep the skin wet to the full dose of prescription and stir evenly and get product.
The present invention also can be used for treating ovary function disease and genital diseases, and the anti-inflammation effect is obvious.Clinical trial shows, the cure rate of milch cow chronic endometritis is reached 88.3%, and total effective rate reaches 98.3%; The present invention uses behind cow or Farrowing in addition, can promote that afterbirth is discharged, uterine involution, helps to shorten calving or farrowing internal, thereby improves the female livestock breed rate.Cure rate to the milch cow retained afterbirth reaches 100%.Convenient drug administration of the present invention, rapid-action, nontoxic non-stimulated, do not cause drug resistance.
The specific embodiment
Embodiment 1
The actual addition of each component of pharmaceutical composition of preparation 1000kg cow endometritis and retained afterbirth prevention and treatment is as follows:
Povidone iodine 2kg
Potassium iodate 0.5kg
Propylene glycol 50kg
Oxytocin 6.77kg (available from Nanjing zoohormone factory)
Carbomer 5kg (available from Beijing compatriots health Science and Technology Ltd. of escaping)
Sodium hydroxide 5kg
Add water to 1000kg
Preparation process is as follows: carbomer is added little water stir, fully swelling; Add sodium hydroxide and make gel-type vehicle; Add povidone iodine again, stir; Potassium iodate adds after being dissolved in little water; To add behind oxytocin and the propylene glycol mixing more at last; Adding water to 1000kg stirs evenly promptly.
Embodiment 2
The actual addition of each component of pharmaceutical composition of preparation 1000kg cow endometritis and retained afterbirth prevention and treatment is as follows:
Povidone iodine 10kg
Potassium iodate 5kg
Propylene glycol 100kg
Oxytocin 10.15kg (available from Nanjing zoohormone factory)
Estrogen 5kg (available from Nanjing zoohormone factory)
Carbomer 1kg (available from Beijing compatriots health Science and Technology Ltd. of escaping)
Sodium hydroxide 2.2kg
Add water to 1000kg
Preparation process is as follows: carbomer is added little water stir, fully swelling; Add sodium hydroxide and make gel-type vehicle; Add povidone iodine again, stir; Potassium iodate adds after being dissolved in little water; To add behind oxytocin, estrogen and the propylene glycol mixing more at last; Adding water to 1000kg stirs evenly promptly.
Embodiment 3
The actual addition of each component of pharmaceutical composition of preparation 1000kg cow endometritis and retained afterbirth prevention and treatment is as follows:
Povidone iodine 20kg
Potassium iodate 10kg
Glycerol 10kg
Oxytocin 0.677kg (available from Nanjing zoohormone factory)
Carbomer 10kg (available from Beijing compatriots health Science and Technology Ltd. of escaping)
Sodium hydroxide 10kg
Add water to 1000kg
Preparation process is as follows: carbomer is added little water stir, fully swelling; Add sodium hydroxide and make gel-type vehicle; Add povidone iodine again, stir; Potassium iodate adds after being dissolved in little water; To add behind oxytocin and the glycerol mixing more at last; Adding water to 1000kg stirs evenly promptly.
Embodiment 4
The actual addition of each component of pharmaceutical composition of preparation 1000kg cow endometritis and retained afterbirth prevention and treatment is as follows:
Povidone iodine 30kg
Potassium iodate 20kg
Glycerol 200kg
Oxytocin 13.536kg (available from Nanjing zoohormone factory)
Estrogen 5kg (available from Nanjing zoohormone factory)
Carbomer 30kg (available from Beijing compatriots health Science and Technology Ltd. of escaping)
Sodium hydroxide 17kg
Add water to 1000kg
Preparation process is with embodiment 3.
Embodiment 5
The actual addition of each component of pharmaceutical composition of preparation 1000kg cow endometritis and retained afterbirth prevention and treatment is as follows:
Povidone iodine 80kg
Potassium iodate 30kg
Propylene glycol 300kg
Propylene glycol 300kg
Oxytocin 2.707kg (available from Nanjing zoohormone factory)
Estrogen 1kg (available from Nanjing zoohormone factory)
Carbomer 40kg (available from Beijing compatriots health Science and Technology Ltd. of escaping)
Sodium hydroxide 25kg
Add water to 1000kg
Preparation process is with embodiment 2.
Embodiment 6
The actual addition of each component of pharmaceutical composition of preparation 1000kg cow endometritis and retained afterbirth prevention and treatment is as follows:
Povidone iodine 20kg
Potassium iodate 40kg
Glycerol 300kg
Oxytocin 10.15kg (available from Nanjing zoohormone factory)
Carbomer 50kg (available from Beijing compatriots health Science and Technology Ltd. of escaping)
Sodium hydroxide 30kg
Add water to 1000kg
Preparation process is with embodiment 3.
Embodiment 7 animal clinical trial examples of the present invention
Utilize the present invention to organize, make positive control, carry out the random packet test with chlortetracycline, oxytetracycline as treatment.The present invention of treatment group as a result is to endometritis cure rate 88.3%, total effective rate 98.3%.Its cure rate is compared difference all extremely significantly (P<0.01) with chlortetracycline group (45%), oxytetracycline group (40%); Total effective rate is significantly higher than chlortetracycline group (65%) and oxytetracycline group (70%) (P<0.05), and treatment group medication number of times obviously is less than two positive controls; Prevention and therapeutic effect to placenta retention are obvious.Conclusion the present invention is definite to the clinical efficacy of endometritis and placenta retention, and administration number of times is few, has no adverse reaction.
Concrete implementation step and effect are:
Trial drug: come from the synthetic pharmaceutical composition of the applicant, (lot number 050329,050404,050405) keeps in Dark Place
Control drug: chlortetracycline (Jin He group in the Inner Mongol produces, lot number 961005); Oxytetracycline (Bei'an, Heilongjiang Province pharmaceutical factory, lot number 930501)
Use apparatus: cattle is used deferent duct; Syringe; Vaginal speculum; Pocket lamp; Routine operation apparatuses such as Baoding rope.
The case source
Test the 8 tame pastures such as friendly dairy industry company first pasture of used milch cow, 199 of total milch cows from the safe cattle farm of Wuhan City, Hubei Province Dongxihu District China, Wuhan friend.Be diagnosed as endometritis through overall health of patients observation, the inspection of vagina prolapsus appliance and examination per rectum.
Diagnostic criteria:
Cow endometritis divides slight, moderate, severe by the state of an illness, and concrete clinical diagnosis standard is:
Slightly: block its property.Flow out the cotton-shaped mucus of volume from eck.Cervical orifice swelling hyperemia, uterus are not seen increase or are slightly increased
Moderate: slight purulent inflammation.Flow out thin yellow-white, yellow green or maroon pus from eck.Cervical orifice swelling hyperemia, uterine volume increases, and the angle inter-drain is not obvious, and uterus hardness increases.
Severe: pyometra.The condensed pus of a large amount of muddy pus is flowed out in cervical orifice height swelling hyperemia, eck, is cheesy sometimes,
Uterine volume obviously increases, and fluctuation is arranged during touch.Stillborn fetus or fetal membrane are detained the secondary infection that causes, visible lochia milch cow placenta retention clinical diagnosis standard: be meant that afterbirth surpasses 8h~12h and fails to discharge after normal labor.
EXPERIMENTAL DESIGN:
Grouping:
Treatment group: suffer from 80 of endometritis milch cow cases.Its mild or moderate 20 examples, moderate 20 examples, severe 20 examples, prevention and treatment placenta retention milch cow 20 examples.
Positive controls: 40 of the total cases of positive controls.
20 of chlortetracycline matched groups are wherein suffered from moderate endometritis 10 examples, severe 10 examples.
Oxytetracycline matched group 20 examples are wherein suffered from moderate endometritis 10 examples, severe 10 examples.
Blank group: have 79 examples
Table 1 is the grouping and the dosage regimen (according to state of an illness grouping, adopting the random packet test) of present embodiment.
Table 1 grouping and processing
Figure C200510019158D00101
Dosage regimen: suffer from cattle and catch up with into cattle pen Baoding, the assistant pulls to a side with oxtail, patient's left hand belt length arm glove, routine disinfection, the left hand the five fingers close up the insertion anus, emptying place excrement is sought cervix uteri and is assisted the right hand that deferent duct is inserted the uterus (because of deferent duct is thinner, easily to insert the uterus, need not to do the cervix uteri the first transaction of a day's business handles), the assistant sends into the uterus with medicine by syringe simultaneously, treats that medicinal liquid flows into the uterus, extracts deferent duct out.Every administration 7 days, drug withdrawal 3 days as 1 course of treatment, when the treatment mild inflammation, is added up by actual frequency if any fully recovering but not reaching as yet for 1 course of treatment.
Curative effect judging standard:
Clinical efficacy is by China's new drug clinical guidance principle regulation, and clinical efficacy divides recovery from illness, produce effects, effective, invalid 4 grades of evaluations.Recovery from illness: clinical symptoms complete obiteration, cervix uteri do not have swelling/hyperemia/hemorrhage, eck, and no rheuminess logistics goes out, the mucus of a small amount of transparent clear of accidental outflow; Straight inspection uterine volume is not seen increase, calm innervation, pain during touch; The uterus softness, the uterine contraction reaction is normal; Produce effects: clinical symptoms obviously alleviates, but not complete obiteration; Effectively: clinical symptoms is apparent slightly to be alleviated, and is tending towards recovering; Invalid: clinical symptoms does not have significant change, and the state of an illness is not seen and alleviated, even occurs worsening; The healing of placenta retention: divide the puerperium to surpass 8h~12h afterbirth and do not discharge, behind successive administration, discharge up to afterbirth.
Observe during the administration and have or not the local excitation reaction after the administration and part or systemic anaphylaxis and recording start time, persistent period, degree, processing through and lapse to etc.Recovery from illness, produce effects are effective case, calculate total effective rate in view of the above.
Statistical procedures: adopt χ 2Medicine reaches the significance of difference with blank group curative effect.
Carry out pharmaceutical composition simultaneously and milch cow is suffered from significance analysis between the group of three kinds of different state of an illness curative effects of endometritis.
Test effect
(1) efficacy analysis between the endometritis group
The treatment group is cured 53 (88.3%), 6 of produce effects (10%), total effective rate 98.3%; The medicine composite for curing group cure rate difference all extremely significantly (P<0.01) of comparing with chlortetracycline group and oxytetracycline group cure rate.Medicine composite for curing group total effective rate is higher than chlortetracycline group and oxytetracycline group, and significant difference (P<0.05) and mean treatment time number average obviously is less than two positive controls.Treatment group milch cow (recovers normal through the other medicines treatment) except that an example produces iodine allergy, other all do not observe whole body or local anaphylaxis and local irritant sense of discomfort.See Table 2.
Table 2 pharmaceutical composition of the present invention and chlortetracycline, oxytetracycline are to the cow endometritis clinical efficacy
The efficacy analysis pharmaceutical composition prevents the evident in efficacy of placenta retention to endometritis and treatment in the endometritis group, and except that an example produced iodine allergy, other cases all had significant curative effect, and total effective rate reaches 100%.Show there was no significant difference (P〉0.05) at the correlation analysis of pharmaceutical composition and milch cow being suffered from the endometritis severity extent.See Table 3.
Table 3 pharmaceutical composition of the present invention is to cow endometritis clinical efficacy in various degree
Figure C200510019158D00121
The placenta retention efficacy analysis: blank group has 79 examples, and wherein 65 smooth calving do not have placenta retention and secondary infection, 14 placenta retention and equal secondary endometritis, placenta retention incidence rate 17.7%, placenta retention secondary endometritis 100%.And make pharmaceutical composition prevention and treatment milch cow placenta retention curative effect that placenta retention and secondary infection obviously all not take place, the extremely outstanding difference (P<0.01) of both existence.See Table 4.
Table 4 medicine composite for curing group of the present invention and blank group are to the prevention and the treatment of milch cow placenta retention
Figure C200510019158D00122
Medication of the present invention is: this pharmaceutical composition directly is filled into intrauterine, one time 50 milliliters, once-a-day, seven days is a course of treatment.

Claims (4)

1, the pharmaceutical composition of a kind of prevention and treatment cow endometritis and retained afterbirth, in parts by weight, its component is as follows:
0.2~10 part of povidone iodine
0.01~4 part of potassium iodate
1~30 part of propylene glycol or glycerol
0.05~1.5 part of oxytocin
0.0~0.5 part of estrogen
0.1~5 part of carbomer
0.2~3 part of sodium hydroxide
Keep the skin wet to 100 parts;
It prepares in accordance with the following methods:
(1) carbomer is added little water and stir, fully swelling;
(2) sodium hydroxide is added in the carbomer of step (1), obtain gel-type vehicle;
(3) povidone iodine is joined in the gel-type vehicle that step (2) obtains, stir;
(4) with little water potassium iodate is made solution and will add in the lump behind oxytocin, estrogen and propylene glycol or the glycerol mixing in the product of step (3) gained;
(5) keep the skin wet to the full dose of above-mentioned prescription.
2, compositions according to claim 1 is characterized in that, in parts by weight, its component is as follows:
0.2~10 part of povidone iodine
0.01~4 part of potassium iodate
1~30 part of propylene glycol
0.05~1.5 part of oxytocin
0.0~0.5 part of estrogen
0.1~5 part of carbomer
0.2~3 part of sodium hydroxide
Keep the skin wet to 100 parts.
3, claim 1 or 2 described a kind of preparation of drug combination methods that are used to prevent and treat cow endometritis and retained afterbirth is characterized in that according to the following step:
(1) carbomer is added little water and stir, fully swelling;
(2) sodium hydroxide is added in the carbomer of step (1) and obtain gel-type vehicle;
(3) stir adding povidone iodine in the gel-type vehicle of step (2), again potassium iodate is dissolved in little water, add in the lump behind oxytocin, estrogen and propylene glycol or the glycerol mixing;
(4) keep the skin wet to the full dose of prescription and stir evenly and get product.
4, claim 1 or the 2 described pharmaceutical compositions application in the pharmaceutical composition of preparation prevention and treatment cow endometritis and retained afterbirth.
CNB2005100191584A 2005-07-25 2005-07-25 Pharmaceutical composition for preventing and curing endometritis and retained afterbirth disease of milk cow Expired - Fee Related CN100493600C (en)

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CN102552104A (en) * 2010-12-18 2012-07-11 广西壮族自治区花红药业股份有限公司 Gel for treating vaginitis and preparation method of gel
CN102657600A (en) * 2012-05-07 2012-09-12 河南省康星药业有限公司 Povidone iodine gel for veterinary use and preparation process
CN103385906B (en) * 2013-07-19 2016-08-10 福建奥姆龙生物工程有限公司 A kind of medicine shortening sow stages of labor and preparation method thereof
CN104906133A (en) * 2015-07-06 2015-09-16 关庆忱 Preparation method of cow postnatal uterus flushing fluid
CN105030660A (en) * 2015-08-11 2015-11-11 张永奎 Temperature-sensitive type gel for curing endometritis of livestock and preparation method for temperature-sensitive type gel
CN114404356A (en) * 2022-01-18 2022-04-29 康膝生物医疗(深圳)有限公司 Temperature-sensitive type slow-release drug-loaded gel preparation for preventing and treating cow endometritis and preparation method thereof
CN114848802B (en) * 2022-05-23 2023-05-09 黑龙江八一农垦大学 Bioactive composition for preventing and/or treating retention of cow placenta, application thereof, powder and tablet

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