CN102552317B - Iodine glycerol nipple infusion and preparation method thereof - Google Patents

Abstract

The invention discloses iodine glycerol nipple infusion and a preparation method thereof. The iodine glycerol nipple infusion provided by invention belongs to local body surface disinfectant, which is composed of iodine, potassium iodide, glycerol, ethanol, sodium chloride and the like. The iodine glycerol nipple infusion prepared by the invention is specifically used for the medicated bath disinfecting of cow nipple skin, and is characterized by wide sterilization spectrum, low effective concentration, quick action speed, steady property, no stimulation, no residual, no harm on people and livestock and being used under a cold and dry weather.

Description

A kind of iodine glycerol nipple preserved material and preparation method thereof

Technical field

The invention belongs to the veterinary drug preparation field, particularly a kind of local body surface disinfectant that is exclusively used in mammilla of milk cattle.

Background technology

The nipple dipping has great importance the prevention mammitis of cow.The method of dipping can use the dipping cup to soak into each nipple separately, also can carry out spray disinfection to nipple with manual sprayer or the flexible pipe that links to each other with press pump in the sterilization pool.The domestic nipple dip that generally uses has povidone iodine, hibitane, sodium hypochlorite, bromo geramine.Advantage is that sterilizing power is strong, and zest is little, but because above-mentioned dip is water solublity, evaporates after the dipping comparatively fast, and acting duration is short, and easily causes the repeated infection of breast.And, can not prevent effectively that skin of nipple from chapping and cold injury in cold exsiccant winter.

The external at present nipple dip that generally uses mostly is the product of iodine glycerol one class, characteristics are that sterilizing power is strong, zest is little, and the effect that nipple is had moist and skin protection, but owing to add ethanol, sodium chloride in the prescription, can not effectively prevent the cold injury after milch cow dipping cold season with antifreezing effect.

Summary of the invention

Based on above reason, the invention discloses a kind of iodine glycerol nipple preserved material, make it to meet the dry cold climatic characteristic of the big province of northern emphasis cowboying such as China Inner Mongol, Heilungkiang, Xinjiang, reduce the sickness rate of mastitis effectively, improve the milking capacity of milch cow.

Iodine glycerol nipple preserved material of the present invention is made up of following component: iodine, potassium iodide, glycerol, ethanol, sodium chloride, purified water.

Described iodine glycerol nipple preserved material, each set of dispense ratio is:

Described iodine glycerol nipple preserved material, each component proportion optimization:

Described iodine glycerol nipple preserved material, its preparation realizes by following technology path:

A, accurately take by weighing iodine and potassium iodide, earlier potassium iodide is dissolved in the suitable quantity of water, add iodine while stirring after treating to dissolve fully, it is dissolved fully, be solution A by recipe quantity;

B, the purified water that takes a morsel, the sodium chloride of adding recipe quantity stirs and makes dissolving, is solution B;

Under C, the stirring, solution A, solution B are mixed, stir;

Add the ethanol of recipe quantity in D, the above-mentioned solution, after stirring makes mix homogeneously, add the glycerol of recipe quantity, stirring is a mix homogeneously;

E, above-mentioned solution are settled to recipe quantity with purified water, stir, promptly.

The invention has the beneficial effects as follows:

1, iodine glycerol nipple preserved material of the present invention, bactericidal effect is good, and is non-stimulated to skin and damaged skin;

2, iodine glycerol nipple preserved material of the present invention has not only kept whole effective ingredient of crude drug, and increase ethanol, sodium chloride with antifreeze effect, and promote the nipple local blood circulation, accelerate water evaporates in the dip, avoid icing in the winter time, cause the cold injury of breast;

3, glycerol can form the oiliness protecting film at skin surface in the component of the present invention, has moist skin, prevents coarse and effect that chap, makes the protected acidic film of skin of nipple intact, resists antibacterial and invades from skin.It can delay the volatilization of iodine in addition, prolongs iodine killing and the inhibitory action time pathogenic microorganism;

4, the present invention is mainly used in the prevention of mammitis of cow, be particularly useful for cold winter, effectively prevent the cold injury of nipple, the sickness rate that makes mastitis is reduced to about 20% from present about 60%, improve whole milk yield and dairy food quality, reduced drug cost.

The specific embodiment:

Embodiment one

Prescription:

Preparation method:

A, accurately take by weighing iodine and potassium iodide, earlier potassium iodide is dissolved in the 100ml water, add iodine while stirring after treating to dissolve fully, it is dissolved fully, be solution A by recipe quantity;

B, get about 50ml purified water, add the sodium chloride of recipe quantity, stir and make dissolving, be solution B;

Under C, the stirring, solution A, solution B are mixed, stir;

Add the ethanol of recipe quantity in D, the above-mentioned solution, after stirring makes mix homogeneously, add the glycerol of recipe quantity, stirring is a mix homogeneously;

E, above-mentioned solution are settled to 1000ml with purified water, stir, promptly.

Embodiment two

Prescription:

Preparation method:

A, accurately take by weighing iodine and potassium iodide, earlier potassium iodide is dissolved in the 100ml water, add iodine while stirring after treating to dissolve fully, it is dissolved fully, be solution A by recipe quantity;

B, get about 100ml purified water, add the sodium chloride of recipe quantity, stir and make dissolving, be solution B;

Under C, the stirring, solution A, solution B are mixed, stir;

Add the ethanol of recipe quantity in D, the above-mentioned solution, after stirring makes mix homogeneously, add the glycerol of recipe quantity, stirring is a mix homogeneously;

E, above-mentioned solution are settled to 1000ml with purified water, stir, promptly.

Embodiment three iodine glycerol nipple preserved material local anaphylaxis and the report of local irritation test

One, material

1, the embodiment of the invention 2 prepared iodine glycerol nipple preserved material.

2, the conventional apparatus of laboratory

3, experimental animal: White Rabbit, body weight 2-3kg; Healthy albino guinea-pig, male and female half and half, body weight 200g～300g.

Two, method

1, intact skin irritant test repeatedly

(1) select 10 of body weight 2～3kg healthy rabbits, 24h before test cuts the hair of rabbit back spinal column both sides, must not injured skin, and unhairing scope, left and right each about 3cm * 3cm.

(2) will be tried direct the dripping in area of thing stock solution 0.5ml next day is on the side unhairing intact skin of 3cm * 3cm, and applies ointment or plaster on a side skin of unhairing surface with 2 layers of onesize gauze, covers the non-stimulated immobilization with adhesive tape of reuse with the non-stimulated plastic foil of one deck then.The opposite side skin of unhairing is as blank.The time of applying ointment or plaster is 4h.After the off-test, remove the residual thing that tried with warm water.

(3) smear 1 every day, smeared continuously 14 days, after smearing 24h, observe at every turn, judge skin irritation intensity.

2, damaged skin irritant test

Select 10 of body weight 2～3kg healthy rabbits, concrete test procedure is as follows:

(1) 24h cuts the hair of rabbit back spinal column both sides before the test, must not injured skin.The unhairing scope, left and right each about 3cm * 3cm.

(2) be coated with tried thing before, on the skin of unhairing of 3cm * 3cm, expose skin with 75% ethanol cleaning, sterilization, after treating the ethanol volatilization, with the damaged wound of injection needle standardized " well " shape in the dermatotome, will be tried thing stock solution 0.5ml and directly be dripped in damage zone, and be applied ointment or plaster at skin surface with 2 layers of onesize gauze, and then cover the non-stimulated immobilization with adhesive tape of reuse with the non-stimulated plastic foil of one deck.Opposite side skin removes dressing and removes the residual thing that tried with warm water in contrast behind the 4h, tried 1h, 24h, 48h behind the thing respectively at removal and observe local skin and react.

Annotate: skin injury only reaches epidermis, does not injure corium.

(3) methods of marking is with an intact skin irritant test.Note differentiating the difference of infection and constitutional irritant reaction,, should carry out retest if there is infection suspicious.

3, skin allergic reaction test

(1) selects the intact healthy albino guinea-pig of skin, male and female half and half, body weight 200g～300g for use.

(2) test grouping: Cavia porcellus is divided into test group, negative control group and positive controls at random, 20 of every treated animals.

(3) before test 24h with unhairing in 3cm * 3cm scope on the left of the guinea pig back.Test group cancellation toxic agent stock solution 0.5ml directly is coated on 2cm * 2cm left side skin of unhairing, and is topped with the non-stimulated plastic foil of one deck, again with non-stimulated immobilization with adhesive tape, continues 6h.7d and 14d in kind repeat once.Positive controls gives positive sensitizer 2, and the 4-dinitrochlorobenzene is induced, the same test group of method.Negative control group is only given normal saline, the same test group of method.

(4) induce back 14d at last, embodiment 2 solution 0.5ml (g) directly are coated on the 2cm * 2cm right side depilation skin, then, with one deck plastic foil and non-stimulated immobilization with adhesive tape, that will apply ointment or plaster behind the 6h is tried the thing flush away.Observe dermoreaction behind 24h and the 48h.

(5) criterion is according to table 1 standard, and the number of animals that dermoreaction (scoring 〉=1) will occur is tried to achieve sensitization rate (%) divided by this group laboratory animal number, presses table 2 evaluation sensitization intensity.

The standards of grading of table 1 dermoreaction

Table 2 sensitization strength grading standard

Annotate: the sensitization rate is 0% o'clock, can be judged to and not see skin allergic reaction.

Three, result

1, iodine glycerol nipple preserved material intact skin irritant test repeatedly

Intact skin irritant reaction result of the test repeatedly: iodine glycerol nipple preserved material was smeared 14 days continuously, observed and smeared position skin, there is no erythema and edema, and the stimulus intensity rank is a nonirritant.

2, damaged skin irritant test

A damaged skin irritant reaction result of the test: embodiment 2 solution are to rabbit damaged skin nonirritant.

3, skin allergic reaction test

Skin allergic reaction result of the test: embodiment 2 solution are to guinea pig skin nonirritant and anaphylaxis.

The dissipation effect test of four pairs of pathogenic microorganisms of embodiment

One, material

1, test medicine: the embodiment of the invention 2 samples;

2, culture medium: martin's bouillon, Martin's agar culture medium etc.;

3, strain: escherichia coli (8099); Staphylococcus aureus (ATCC6538); Hemolytic streptococcus C type; Candida albicans (ATCC10231), Military Medical Science Institute provides by Beijing.

4, virus: swine fever lapinized virus, lyophilizing swine fever virus cell culture vaccine, newcastle disease I are virus, are provided by microorganism teaching and research room of Agricultural University of the Inner Mongol.

5, experimental animal: 15 of White Rabbits, body weight 1.5-2.0kg, male and female is not limit; The non-immune Embryo Gallus domesticus of 10 ages in days.

Two, method

1, quantitatively tries face

Method is carried out according to " disinfectant for animals authenticate technology standard ".The bacteria containing amount of test organisms liquid is respectively: staphylococcus aureus 3.2 * 10⁵CFU/ml, Hemolytic streptococcus 2.7 * 10⁵CFUlml, escherichia coli 8.4 * 10⁶CFU/ml, Candida albicans bacteria containing amount 2.6 * 10⁵CFU/ml.Test repeats 3 times.

2, to the test of killing of swine fever virus

Getting 4.5mL embodiment 2 mixes with swine fever lapinized virus (being equivalent to 10,000 rabbit minimal infecting dose (MID)s) 0.5mL and puts preheating 5min in 20 ℃ of water-baths, 10min (matched group is a normal saline), get the solution 1mL in above-mentioned each test tube respectively, add nertralizer 9mL, mixing, effect 10min, carry out doubling dilution, each inoculation of each dilution factor contains 5 of the cell culture tubes of slide, cultivates 4 days for 37 ℃, check the fluorescence production with fluorescent staining method, statistics inactivation of virus rate.

3, Avian pneumo-encephalitis virus is killed test

(every milliliter contains virus 10 to get the fresh Embryo Gallus domesticus liquid that contains newcastle disease virus⁹EID50) 2.5mL adds among the 2.5mL embodiment 2, mixing, and 20 ℃ of water-baths act on 10min and 30min respectively, get the above-mentioned mixed liquor of 0.5mL respectively and add in the 4.5mL nertralizer, mixing, effect 10min.Get above-mentioned solution, the injection chick embryo allantoic cavity, every embryo 0.2mL gets blastochyle and does blood clotting (HA) test behind the 24h.The inactivation ratio of statistics virus.

Three, result

1, quantitative test

The results are shown in Table 1.

The killing action effect of table 1 pair antibacterial

Annotate: the result is 3 test meansigma methodss.

Experimental result shows: action time, sterilizing rate all can reach 100% more than 2min, on average killed index greater than 10⁵

2, the test of killing the virus

The results are shown in Table 2.

The killing effect of table 2 pair virus

Test shows: effect 5min, 10min, the killing rate of swine fever virus and newcastle disease virus is 100%, and reach the requirement of " disinfectant for animals authenticate technology standard ".

The clinical experiment report of embodiment pentaiodo glycerol nipple preserved material

The test of the clinical disinfection of iodine glycerol nipple preserved material be with mammilla of milk cattle surface adhesion antibacterial as sterilization objects, with the prevention mastitis, the protection breast is the test that purpose is carried out.The milking station on ground such as selective call and hot suburban area, Tu Zuoqi and Xi Meng is as the testing site, and test period is chosen in Various Seasonal, in order to observe the influence of climate change to Disinfection Effect, especially observes disinfectant Disinfection Effect in the winter time.

On-site disinfection test

One, material

1, iodine glycerol nipple preserved material: embodiment 2, dilution is 4 times during use.

2, commercially available betagen solution contains available iodine 1.0%, lot number: 20040912.

3, culture medium: martin's bouillon, Martin's agar culture medium etc.

4, Tween 80: medicinal, lecithin: medicinal, Na₂S₂O₃: analytical pure.

Two, method

1, grouping:

Selective call and hot suburban area close woods milking station (first testing site), and room milking station of native left flag (second testing site) and stannum alliance milking station (the 3rd testing site) are tested.Each milking station selects 50 cow heads, with 2 nipples in every cow head left side as iodine glycerol nipple preserved material sterilizing test nipple (the 1st group), right front nipple is as betagen solution contrast sterilizing test nipple (the 2nd group), and right back nipple uses distilled water as blank (the 3rd group).Test period is respectively April, August and December in 2005.

2, method:

(1) dosage: the embodiment 2 that dilutes 4 times uses liquid; Betagen solution is made into the use liquid of 0.5% (containing available iodine); Blank group sterile saline.

(2) sampling before the sterilization: with four nipples of milch cow as sampled point, the cotton swab that soaked into nertralizer is in (each wiping 3 times anyhow of 5cm * 5cm) of nipple and surrounding skin, and the wiping surface of conversion cotton swab, the Cotton Gossypii section of cotton swab of will sterilizing is then inserted in the test tube that contains the 5mL sterile saline, concussion, standby.

(3) sterilization: after milch cow is milked end, use liquid, 0.5% betagen solution and distilled water that the different nipples of milch cow are carried out 15-20 with the embodiment 2 of 4 times of dilutions respectively and dip sterilization second, and smear surrounding skin, the about 5cm of area * 5cm size with disinfecting cotton swab.

(4) sterilization post-sampling: behind the milk cow sterilizing, make it free movable, sampling in 10 minutes, 4 hours, 8 hours, 12 hours, 16 hours, 20 hours, 24 hours, method was the same respectively.Observe skin of nipple and have or not abnormal conditions such as red, swollen, hot, pain.

(5) sample treatment and viable bacteria metering: from every duplicate samples, get 1mL, add the 9mL nertralizer respectively,, make 10 * doubling dilution with sterile saline at 25 ℃ of effect 10min.The dilution sample of difference is seeded in Martin's agar culture medium respectively, puts in 37 ℃ of calorstats and cultivate, each dilution factor is made two plates.Take out after 48 hours and carry out colony counting.Select the plate clump count to count 30-300 person, and count results is converted into the viable count of 5mL stock solution, error rate surpasses 10% reform.

Clump count * 100% before sterilization rate=(clump count after the clump count-sterilization before the sterilization) ÷ sterilization

Three, result

The results are shown in Table 3.

Table 3 on-site disinfection test result

Annotate: 1^*: embodiment 2 sterilization groups; 2^*: 0.5% betagen solution sterilization group; 3^*: the blank group.

On-site disinfection test shows: dipping sterilization after milking with 2 pairs of milch cows of embodiment of 4 times of dilutions, and 10min, 4h, 8h, 12h sterilization rate are 100% after sterilization; Sterilization rate reduces gradually in back 16-24 hour though sterilize, but still remains on more than 90.0%.Seasonal variations does not have obvious influence to Disinfection Effect.In addition, the nipple local skin there is not bad stimulation.Sterilize with method with 0.5% betagen solution, 10min, 4h sterilization rate are 100% after sterilization, and sterilization rate reduces gradually in 6-24 hour after sterilization, and sterilization rate is between 50%-90%; Blank group viable count before and after sterilization does not have significant change.

What should particularly point out here is: stannum alliance test group is under-20 ℃ of weather conditions, and iodine glycerol nipple preserved material still keeps bactericidal effect preferably, and the dipping rear udder attachment does not have cold injury.Betagen solution then has iodine to separate out under the temperature of cold, and effectively sterilizing time obviously shortens, and the time that does not have iodine glycerol nipple preserved material to continue is long.The blank group has icing phenomenon at nipple and surrounding skin, causes the breast cold injury.

Preventive effect to mastitis

With iodine glycerol nipple preserved material mammilla of milk cattle is carried out dipping, the sickness rate of statistics mastitis is observed the preventive effect of disinfectant to mastitis.

One, material

1, the embodiment of the invention 2 samples;

2, betagen solution: contain available iodine 1.0%, lot number: 20040912.

3, CMT-Test reagent.

Two, method

1, test grouping: select 3 of the milking station of milch cow number about 500 at the Huhehaote suburban area, establish embodiment 2 dipping groups, betagen solution dipping group and blank group respectively.Dipping is 3 months continuously, relatively the incidence rate of mastitis before and after the dipping.

2, dipping method: the dipping cup of respectively embodiment 2 solution, 0.5% betagen solution being packed into, the medicinal liquid height remains on more than the 5cm, soaks libation at an ancient wedding ceremony mammilla of milk cattle 15-20 second, and smear surrounding skin with disinfecting cotton swab, dipping after at every turn milking, one day twice, continuous 3 months.The blank group compares with distilled water.

3, inspection method: after four breast district sterilizations totally of milch cow, discard former milk, each nipple divides don't push 3 milliliters of milk then, insert and have graduated four round ware vinyl discs, draw equivalent CMT-Test reagent with suction pipe then, splash in the round ware milk, all around slowly incline and shake, observation test result after 1 minute.The milk thickness in the pasty state or to have floccule to occur then positive, promptly be diagnosed as latent mammitis, have simultaneously that affected part breast district is solid concurrently, swelling, pain, slight fever, excretory milk is butyrous, or contain the pus piece of foul smell, or thin milk, be studded with that grumeleuse, flocculent deposit person are diagnosable to be the dominance mastitis.In addition the observed and recorded skin of nipple have or not rough, chap, pimple etc.

Three, result

1, disinfectant is to the preventive effect of mastitis

The results are shown in Table 4.

Table 4 disinfectant is to the preventive effect of mastitis

To the continuous dipping of mammilla of milk cattle 3 months, can make the incidence rate of subclinical mastitis descend 53.9% with embodiment 2 solution, the incidence rate of dominance mastitis descends 23.6%, and the prevention mastitis are had a significant effect.

Betagen solution can make the incidence rate of subclinical mastitis descend 45.5%, and the incidence rate of dominance mastitis descends 18.9%, also have preventive effect preferably, but the effect of embodiment 2 is then better.

2, disinfectant is to the protective effect of skin of nipple

The results are shown in Table 5.

Table 5 disinfectant is to the protective effect of skin of nipple

With embodiment 2 solution and betagen solution to the continuous dipping of mammilla of milk cattle 3 months, can effectively prevent skin of nipple rough, chap and the generation of pimple, do not have notable difference between the two.

Antifreeze effect test after the dipping of embodiment hexaiodo glycerol nipple preserved material

One, material

1, the embodiment of the invention 2 iodine glycerol nipple preserved material.

2, iodine glycerol solution (by " Chinese veterinary drug allusion quotation version in 2005 " standard production) contains available iodine 1.0%, lot number: 20051001.

3, commercially available betagen solution: contain available iodine 1.0%, lot number: 20050712.

Two, method

1, test site: Xi Meng hot milking station.

2, test period :-14 days on the 12nd January in 2006.

3, outside air temperature :-25 ℃, cowshed temperature-20 ℃

4, test grouping: select 80 cow heads altogether, 20 every group, embodiment 2 solution (the 1st group), iodine glycerol solution (the 2nd group), betagen solution (the 3rd group), blank (the 4th group).

5, test method:

(1) dosage: the embodiment 2 of 4 times of dilutions uses liquid; 0.5% (containing available iodine) iodine glycerol uses liquid, the use liquid of 0.5% (containing available iodine) povidone iodine; Blank group sterile saline.

(2) dipping method: the dipping cup of respectively embodiment of the invention 2 use liquid, 0.5% iodine glycerol solution, 0.5% betagen solution of 4 times of dilutions being packed into, the medicinal liquid height remains on more than the 5cm, dips mammilla of milk cattle 15-20 second, the back dipping of at every turn milking.The blank group compares with distilled water.Milch cow gets back to cowshed after milk Room dipping.

The etat mammelonne result is observed in (3) four groups of continuous dippings of milch cow after 3 days, the nipple cold injury is meant that the nipple performance is red, swollen, hot, the symptom of pain.

Three, result

The results are shown in Table 6.

Observe the etat mammelonne result after the table 6-20 ℃ nipple dipping

The result as seen, under-20 ℃ of weather conditions, continuously dipping is after 3 days, embodiment 2 solution character are stable, no iodine is separated out, the dipping rear udder attachment does not have cold injury.Iodine glycerol solution, betagen solution then under the temperature of cold solution have iodine to separate out, at nipple and surrounding skin icing phenomenon is arranged, cause the breast cold injury.As seen the present invention has tangible antifreezing effect.

Claims (3)

1. iodine glycerol nipple preserved material is characterized in that each set of dispense ratio is:

Iodine 1.0-2.5% W/V;

Potassium iodide 1.0%-2.5% W/V;

Ethanol 30%-50% W/V;

Sodium chloride 2%-5% W/V;

Glycerol 25%-45% W/V;

Purified water adds to 100% V.

2. a kind of iodine glycerol nipple preserved material as claimed in claim 1 is characterized in that each set of dispense ratio is:

Iodine 2.0% W/V;

Potassium iodide 2.0% W/V;

Ethanol 40% W/V;

Sodium chloride 3% W/V;

Glycerol 35% W/V;

Purified water adds to 100% V.

3. the preparation method of an iodine glycerol nipple preserved material as claimed in claim 1 or 2, realize by following technology path:

A, accurately take by weighing iodine and potassium iodide, earlier potassium iodide is dissolved in the suitable quantity of water, add iodine while stirring after treating to dissolve fully, it is dissolved fully, be solution A by recipe quantity;

B, the purified water that takes a morsel, the sodium chloride of adding recipe quantity stirs and makes dissolving, is solution B;

Under C, the stirring, solution A, solution B are mixed, stir;

Add the ethanol of recipe quantity in D, the above-mentioned solution, after stirring makes mix homogeneously, add the glycerol of recipe quantity, stir and make mix homogeneously;

E, above-mentioned solution are settled to recipe quantity with purified water, stir, promptly.