CN110063976B

CN110063976B - Spray for preventing newborn piglet asphyxia and preparation method thereof

Info

Publication number: CN110063976B
Application number: CN201910371373.2A
Authority: CN
Inventors: 夏兴建; 郭威; 张敏; 殷中兰; 曹伟伟; 马晓燕; 陈秋萍; 杨家飞; 濮国群; 刘文进; 李会芳
Original assignee: Individual
Current assignee: Individual
Priority date: 2019-05-06
Filing date: 2019-05-06
Publication date: 2021-07-20
Anticipated expiration: 2039-05-06
Also published as: CN110063976A

Abstract

A spray for preventing newborn piglet asphyxia and a preparation method thereof, wherein each 100g of the spray comprises the following components by weight: 0.01-0.5 g of benzalkonium bromide, 0.05-2.0 g of tannic acid, 0.01-3.0 g of mustard oil, 1882.0-6.0 g of poloxamer, TX-10010.0-20.0 g of emulsifier, 5.0-10.0 g of isopropanol and the balance of deionized water. The spray of the invention has obvious asphyxia-preventing effect on newborn piglets. When in use, the spray is sprayed to nostrils and oral cavity of newborn piglets, so that residual amniotic fluid and mucus in the air outlet pipe, nasal passage and oral cavity can be rapidly discharged, asphyxia caused by blockage can be prevented, and the spray also has a prevention effect on pathogens infected by respiratory tract. The invention further discloses a preparation method of the compound, which has strong process operability, low cost, contribution to production conversion and wide market prospect.

Description

Spray for preventing newborn piglet asphyxia and preparation method thereof

Technical Field

The invention belongs to the technical field of veterinary medicines, and particularly relates to a spray for preventing newborn piglets from suffocating and a preparation method thereof.

Background

The asphyxiation of the newborn piglets is a common phenomenon in pig raising production, and most of the phenomenon is that after the piglets are born, amniotic fluid and mucus in the trachea, nostrils or oral cavity cannot be discharged in time to block respiratory tracts, external air cannot enter the lung, at the moment, the umbilical cords are broken, blood cannot obtain enough oxygen, and finally the piglets are asphyxiated to death. The common method for preventing asphyxia in clinic is to carry out artificial respiration on piglets, and the specific method is that the left hand and the right hand respectively hold the neck and the hip of the piglet, continuously flex and stretch along the direction of the large curve of the abdomen, passively expand and contract the lung by virtue of external force, and force the blockage in the trachea, the nasal passage and the oral cavity to be discharged, so that air smoothly enters the lung, and the problem of asphyxia is solved.

Practice shows that the artificial respiration method wastes time and energy, the operation needs certain skills, amniotic fluid or mucus can be sucked into the lung reversely if the operation is not proper, respiratory tract infection is caused, meanwhile, the survival of piglets can not be completely guaranteed by the artificial respiration method, and the clinical rescue success rate can reach 70 percent, which is a relatively high level. In large pig farms, sows are in estrus and parturient at the same time, and the time of delivery is concentrated at the same time. A lot of piglets facing suffocation exist in the delivery period, hands are often insufficient at the moment, artificial respiration consumes long time, and finally, part of newborn piglets die due to oxygen deficiency, so that certain economic loss is brought to a pig farm.

At present, no product specially aiming at preventing the asphyxia of the newborn piglets appears in the market for a while. In order to fill the market blank, the spray for preventing the asphyxia of the newborn piglets is prepared by only spraying the nasal opening and the oral cavity of the newborn piglets when the piglets are born, the piglets can actively sneeze and cough under the stimulation of liquid medicine, and residual amniotic fluid and mucus in the trachea, the nasal opening and the oral cavity are quickly discharged under the impact of high-speed airflow, so that the aims of breathing air in time and preventing the asphyxia are fulfilled.

Besides the anti-asphyxia function, the spray of the invention can cause a plurality of receptor proteins on the surface of the nasal mucosa to have temporary conformation change, so that the receptor proteins can not be identified by external pathogens, and the pathogens in the environment can not be specifically combined after invading the nostrils, thereby avoiding infection and indirectly playing a certain role in preventing diseases transmitted through the respiratory tract.

Disclosure of Invention

The invention aims to provide a spray for preventing newborn piglets from suffocating, and a preparation method thereof is another object of the invention.

Based on the purpose, the invention adopts the following technical scheme: a spray for preventing newborn piglet asphyxia and a preparation method thereof, wherein each 100g of the spray comprises the following components by weight: 0.01-0.5 g of benzalkonium bromide, 0.05-2.0 g of tannic acid, 0.01-3.0 g of mustard oil, 1882.0-6.0 g of poloxamer, TX-10010.0-20.0 g of emulsifier, 5.0-10.0 g of isopropanol and the balance of deionized water.

Preferably, per 100g of the spray comprises 0.1-0.3 g of benzalkonium bromide, 0.5-1.5 g of tannic acid, 0.1-2.0 g of mustard oil, 1883.0-5.0 g of poloxamer, TX-10012.0-18.0 g of emulsifier, 7.0-9.0 g of isopropanol and the balance of deionized water.

More preferably, the weight of each 100g of spray comprises 0.2g of benzalkonium bromide, 1.0g of tannic acid, 1.0g of mustard oil, 1884.0 g of poloxamer, TX-10015.0 g of emulsifier, 8.0g of isopropanol and 70.8g of deionized water.

The deionized water is sterilized deionized water.

The spray agent of the invention is a light yellow opaque emulsion with uniform texture.

The preparation method of the spray for preventing the asphyxia of the newborn piglets comprises the following steps: (a) adding poloxamer 188 into emulsifier TX-100, continuously stirring until poloxamer 188 is completely dissolved, adding isopropanol, and stirring uniformly to obtain system A; (b) adding mustard oil into the system A, and uniformly stirring to obtain a system B; (c) mixing tannic acid and benzalkonium bromide, and adding the rest of deionized water to completely dissolve the tannic acid and the benzalkonium bromide to obtain a system C; (d) and (3) gradually adding the system C into the system B, emulsifying the mixed system by using an emulsifying machine while adding, gradually turning the system from clear to turbid, finally forming a light yellow opaque emulsion with uniform texture, and sealing and subpackaging to obtain the product.

The usage and dosage are as follows: the spray is aimed at the nostrils and the oral cavity of the newborn piglets for 1-3 times.

The invention has reasonable formula, safe use for newborn piglets and definite clinical use effect, can obviously reduce the death of piglets caused by asphyxia, and simultaneously has obvious prevention effect on pathogens infected by respiratory tract.

In the formula of the invention, the components have the following effects:

1) the benzalkonium bromide is a cationic surfactant, can change the permeability of bacterial cytoplasmic membrane, make the bacterial cytoplasmic substance exosmose, block its metabolism and kill it. After the nasal spray is used, the bacterial pathogen can be prevented from infecting respiratory tract, and nasal cavity can be purified.

2) The tannic acid can be sprayed to deposit on the surface of the nasal mucosa to play a certain protection role on the nasal mucosa, and simultaneously, the tannic acid can be combined with proteins on the surface of mucosal cells to cause the proteins to have temporary conformational changes, including but not limited to specific binding receptor proteins of pathogens infected by respiratory tract routes. After the space conformation of the receptor protein is changed, the pathogen can not normally recognize the receptor protein, the receptor protein can not be specifically combined, and the piglet can not be infected, thereby playing a certain role in protection.

3) The mustard oil is light red oily liquid obtained by distilling yellow mustard seeds at high temperature, has pungent taste, has certain irritation to respiratory mucosa and oral mucosa, is temporary, and only lasts for tens of seconds after being contacted, and has the function of promoting active sneezing and coughing of piglets. The high-speed airflow generated during sneezing and coughing can discharge residual amniotic fluid and mucus in trachea, oral cavity and nasal passage, so as to make breathing smooth, thereby preventing asphyxia.

4) Poloxamer 188 and an emulsifier TX-100 are selected, both are emulsifiers, and the hydrophilic-lipophilic balance value obtained after compounding is the same as or close to the hydrophilic-lipophilic balance value required by emulsification of mustard oil, and the two are matched to form stable mustard oil emulsion. Meanwhile, the two are mild in nature to trachea, oral cavity and nasal mucosa, have a buffering effect on pungent taste of mustard oil, avoid over stimulation and are safe to use.

5) The selected isopropanol can play a role in emulsification assistance on one hand, and has a certain solubilization role in benzalkonium bromide, tannic acid and mustard oil on the other hand, so that unstable conditions such as precipitation and the like in the later-period storage process of the medicine are avoided. In addition, the isopropanol can enhance the fluidity of the system and is beneficial to spraying.

Besides the advantages of the formula, the invention has simple process, strong operability, low manufacturing cost, contribution to large-scale popularization in the field of pig raising and wider market prospect, and can be produced without introducing high-end and expensive equipment.

Compared with the existing artificial respiration method for preventing the piglet asphyxia, the artificial respiration method has the following effects:

1) the spray can obviously stimulate newborn piglets to sneeze and cough actively, and can discharge amniotic fluid and mucus blocked in trachea, oral cavity and nasal passage rapidly by airflow. The operation is simple, the time and the labor are saved, even a new worker without midwifery experience can easily learn to save a suffocating piglet only in a few seconds, and the traditional artificial respiration method can require several minutes or even tens of minutes.

2) The spray has more exact effect, the effective rate can reach more than 90% proved by clinic, the effective rate of clinical statistics of the traditional method is approximately between 30% and 70%, the effective rate of experienced midwife is high, and most newborn piglets die finally for inexperienced midwives.

3) After the spray disclosed by the invention is sprayed, the protein receptor space conformation of nasal mucosa epithelial cells can be reversibly and temporarily changed, so that the nasal mucosa epithelial cells cannot be identified by pathogens in the environment, and the incidence rate of diseases infected by respiratory tract approaches, such as infection of pseudorabies viruses, respiratory coronavirus, actinobacillus pleuropneumoniae and other pathogens, is reduced.

4) After the invention is used, the antibacterial component in the feed additive can purify bacterial pathogens in respiratory tract and oral cavity in early stage, thereby reducing the morbidity of bacterial diseases and being beneficial to the later growth of piglets.

5) The preparation process has strong operability, is beneficial to conversion, and has low cost of the prepared medicine, high farm acceptance and easy clinical popularization.

Detailed Description

The present invention will be specifically illustrated by the following examples, but these specific embodiments do not limit the scope of the present invention in any way.

Examples 1 to 11

In order to make the description more concise, the weight compositions of the sprays for preventing asphyxia of newborn piglets described in examples 1-11 are given in the form of tables, the total weight of each example is 100g, and the specific compositions are shown in table 1.

TABLE 1 weight composition of a spray for preventing asphyxia of newborn piglets

The preparation method of the spray for preventing the asphyxia of the newborn piglets, which is described in the embodiment 1, comprises the following steps:

(a) adding 4.00g of poloxamer 188 into 15.0g of emulsifier TX-100, continuously stirring until the poloxamer 188 is completely dissolved, adding 8.0g of isopropanol, and uniformly stirring to obtain a system A;

(b) adding 1.0g of mustard oil into the system A, and uniformly stirring to obtain a system B;

(c) mixing 1.0g of tannic acid and 0.2g of benzalkonium bromide, adding 70.8g of deionized water, and stirring to completely dissolve to obtain a system C;

(d) and (3) gradually adding the system C into the system B, emulsifying the mixed system by using an emulsifying machine while adding, gradually becoming turbid from clarification to finally form a light yellow opaque emulsion with uniform texture, and sealing and subpackaging to obtain the spray of the invention.

The specific procedures of examples 2-11 are the same as those of example 1.

Test example 12 stability of Properties of inventive products

The inventive examples 1 to 11 were sampled, and the samples were placed at room temperature (outside temperature 15 to 25 ℃), at high temperature and high humidity (temperature 40 ℃ and relative humidity 75%) at an accelerated speed, at 4 ℃ and at a low temperature of-20 ℃ and frozen. The appearance properties of the samples of the embodiments are respectively sampled and observed at 0d, 15d, 30d, 90d, 180d and 360d after the test, and the results show that the samples placed at normal temperature, accelerated placement and low temperature have no phenomena of layering, color change, drug precipitation and the like, the frozen samples are frozen, but have no phenomena of layering, color change, drug precipitation and the like after being melted again at the temperature, and the properties are stable.

And (4) test conclusion: the product of the invention has better stability.

Test example 13 safety test

The safety of the invention to newborn piglets is verified by clinical trials as follows.

16 healthy newborn piglets were selected and randomly divided into 1, 2, 3 and 4 groups of 4 piglets, each of which was half of a male parent. Wherein group 1 is a control group without any drug, and groups 2, 3 and 4 are test groups, and the liquid medicine of the present invention is sprayed to the oral cavity and nostril at the first time after birth. The liquid medicine of the invention in example 1 was filled into a spray bottle, the 2 nd group of test piglets were sprayed 1 time each on the oral cavity and nasal cavity, respectively, the same procedure was carried out, and the 3 rd and 4 th group of piglets were sprayed 5 times and 10 times each, respectively, to verify the safety of the medicine by comparison. All piglets are raised in the same environment and raised in the same management mode. The test pigs were observed for inflammatory reactions and lesions of nasal and oral mucosa at 1h, 2h, 3h, 5h, 10h, 24h, 48h and 72h after administration, respectively, and if they showed no difference from the control group 1, they were good and were recorded with the "√" mark. The behavior and activity and death of the pigs were observed and recorded carefully during the test period, and the results are shown in Table 2.

Table 2 clinical safety test of spray for preventing asphyxia of newborn piglets according to the present invention

Numbering

1h

2h

3h

5h

10h

24h

48h

72h

Group 1

√

Group 2

√

Group 3

√

Group 4

√

Note: ("√" indicates good, undamaged nasal and oral mucosa)

And (3) test results:

1) mucosal damage: the mucosa of the test pigs in the groups 2, 3 and 4 has no inflammatory pathological characteristics of red, swelling, heat, pain and dysfunction after 1h, 2h, 3h, 5h, 10h, 24h, 48h and 72h of the application, and has no difference with the group 1 of the control group;

2) the test pigs in each group have no death, the behavior is normal, and the behavior is not obviously different from that of the 1 st group in the control group;

3) each group of test pigs has no other toxic clinical manifestations;

and (4) test conclusion: the spray of the invention is safe for newborn piglets.

Test example 14 Pseudorabies Virus infection blocking test

Pseudorabies is an acute contact infectious disease of pigs, is caused by pseudorabies virus infection, mainly attacks the nervous system of piglets, and can greatly affect the reproductive system after sow infection to cause reproduction disorder. The disease is mainly transmitted through respiratory tract, the nostril is an important entrance of virus infection, after the virus invades nasal mucosa, the virus is firstly combined with a protein receptor on the surface of the mucosa and then further invades submucosa to form viremia, and then the whole body infection is caused to cause the disease. After the spray is used, the pseudorabies virus receptor protein on the nasal mucosa surface of the piglet can be subjected to temporary conformation change, the denatured protein receptor can not be identified after virus invasion, and further infection can not be formed, so that the protective effect is achieved.

20 newborn piglets were randomly selected and divided into two groups, 10 piglets each, and half of the female and male piglets. The first group was a positive control group, which was infected by forced nasal drip with a cell culture solution containing pseudorabies virus. The second group is a test group, the spray of the invention is firstly sprayed to the nostrils, after waiting for 2 hours, the cell culture fluid containing pseudorabies virus is forcibly dripped into the nose, and the infection condition is observed. All test pigs were kept in the same environment and were kept in the same management mode. After pseudorabies virus infection, the incubation period is usually 3-5 days, and then symptoms begin to appear. For the accuracy of the test data, the test period is set as one week, and the clinical manifestations and death conditions of the pigs are observed every day during the test period, and the morbidity and the mortality are counted. After the test is finished, blood of the pig is extracted for PCR molecular biology identification of the virus, if infection exists, the result of nucleic acid amplification is positive, otherwise, the result is negative, and a record is made during the test. The results are shown in Table 3.

TABLE 3 blocking test of pseudorabies virus infection by spray for preventing asphyxia of newborn piglets according to the present invention

	Number of sick pigs/pig	Incidence rate/%)	Number of dead pigs/pig	Mortality rate/%)
					Group 1	9	90	7	70
Group 2	2	20	1	10

After the test is finished, the detection results of all the porcine blood viruses are as follows:

the detection results of 9 diseased patients in the first group are all positive, which indicates infection, and the results of 1 non-diseased patient are negative and are not infected;

the detection results of 2 diseased patients in the second group are positive, which indicates infection, and the results of 8 non-diseased patients are negative and are not infected;

the result of comparison between the test group and the control group shows that the infection rate of pseudorabies virus invaded through the nasal cavity can be reduced by 70 percent, and the death rate can be reduced by 60 percent.

And (4) test conclusion: the spray for preventing the newborn piglet asphyxia has a good prevention effect on the pseudorabies.

Example 15 drug efficacy test

The invention mainly stimulates the nerve cells of oral cavity and nostril of the piglet instantly to promote the newborn piglet to sneeze and cough actively, and flushes out the residual amniotic fluid and mucus in trachea, oral cavity and nasal passage under the condition of rapid air flow, thereby rapidly ensuring the smooth respiration of the newborn piglet and preventing asphyxia.

8 experimental pigs in the same litter are randomly selected and divided into two groups, wherein each group comprises 4 pigs and half pigs. Group 1 was the test group, four pigs were marked 1-1, 1-2, 1-3 and 1-4 respectively, after the piglets were born and sprayed with the spray prepared in example 1 of the present invention, once in the nostrils and mouth, after which the piglets were observed for sneezing and coughing, at intervals of 20s, recorded times, and recorded for 140 s. Group 2 was a control group, four pigs were designated 2-1, 2-2, 2-3 and 2-4, respectively, and 4 piglets in the control group were sprayed with the same amount of physiological saline in the same manner in order to reduce the effect of physical irritation and stress due to the spray on the test results, and the number of sneezes and coughs was recorded. All test pigs were kept in the same environment and were kept in the same management mode. The results of the sneezing and coughing events are reported in tables 4 and 5.

TABLE 4 test of the number of sneezing of pigs at various time intervals after application of the sprays of the invention

As can be seen from Table 4:

the 4 pigs in the experimental group sneezed 40 times in total within 140s, with an average of 10 times per pig, all concentrated within the first 100s, after which there was no longer a sneeze.

The 4 pigs in the control group sneezed a total of 3 times within 140s, with an average of 0.75 times per pig, all centered within the first 20s, after which no further sneezing occurred.

Remarking: the normal saline itself has no inductive stimulation effect on the nasal mucosa, and the sneezing behavior of the pigs in the control group is probably related to the physical impact and the stress reaction of the nasal mucosa by the water pressure after the normal saline is sprayed.

TABLE 5 test of the number of coughs in pigs at various time periods after administration of the spray of the invention

As can be seen from Table 5:

the 4 pigs in the experimental group showed a total of 50 coughs within 140s, with an average of 12.5 coughs/pig, all concentrated within the first 120s, after which there was no longer any coughing behavior.

The 4 pigs in the control group had 2 coughs within 140s, only 2-2 and 2-4, and the other two had no coughs, with an average number of 0.5 per pig overall, centered within the first 20s, after which there was no longer coughs.

Remarking: the normal saline itself has no effect of inducing the pig cough, and the pig cough behavior of the control group is probably related to the physical impact of water pressure on the throat part and the stress reaction after the normal saline is sprayed.

The results show that: the piglets in the test group showed significantly more sneezing and coughing than in the control group.

And (4) test conclusion: the spray for preventing the newborn piglet asphyxia has the obvious effect of inducing the newborn piglet to sneeze and cough.

Claims

1. The spray for preventing the asphyxia of the newborn piglets is characterized in that each 100g of the spray comprises the following components in parts by weight: 0.01-0.5 g of benzalkonium bromide, 0.05-2.0 g of tannic acid, 0.01-3.0 g of mustard oil, 1882.0-6.0 g of poloxamer, TX-10010.0-20.0 g of emulsifier, 5.0-10.0 g of isopropanol and the balance of deionized water.

2. The spray for preventing asphyxia of newborn piglets according to claim 1, wherein the spray comprises, by weight per 100g, benzalkonium bromide 0.1-0.3 g, tannic acid 0.5-1.5 g, mustard oil 0.1-2.0 g, poloxamer 1883.0-5.0 g, emulsifier TX-10012.0-18.0 g, isopropanol 7.0-9.0 g, and the balance deionized water.

3. The spray for preventing asphyxia of newborn piglets according to claim 2, wherein the weight per 100g of the spray consists of: 0.2g of benzalkonium bromide, 1.0g of tannic acid, 1.0g of mustard oil, 1884.0 g of poloxamer, TX-10015.0 g of emulsifier, 8.0g of isopropanol and 70.8g of deionized water.

4. The spray for preventing asphyxia of newborn piglets according to claim 1, 2 or 3, wherein the deionized water is sterilized deionized water.

5. The preparation method of the spray for preventing the asphyxia of the newborn piglets as claimed in any one of claims 1, 2 or 3, which is characterized by comprising the steps of: (a) adding poloxamer 188 into emulsifier TX-100, continuously stirring until poloxamer 188 is completely dissolved, adding isopropanol, and stirring uniformly to obtain system A; (b) adding mustard oil into the system A, and uniformly stirring to obtain a system B; (c) mixing tannic acid and benzalkonium bromide, and adding the rest of deionized water to completely dissolve the tannic acid and the benzalkonium bromide to obtain a system C; (d) and (3) gradually adding the system C into the system B, emulsifying the mixed system by using an emulsifying machine while adding, gradually turning the system from clear to turbid, finally forming a light yellow opaque emulsion with uniform texture, and sealing and subpackaging to obtain the product.