CN118078746B - Matrine back-watering solution for expelling parasites of cattle and sheep and preparation method and application thereof - Google Patents

Abstract

The application provides matrine back solution for expelling parasites in cattle and sheep, and a preparation method and application thereof, belonging to the technical field of livestock and poultry pharmaceutical preparations; matrine and alliin with definite curative effect are taken as main active components, rice vinegar and menthol are used for promoting permeation, and specific percutaneous absorption raw materials of triolein and ethylene glycol are matched and water is taken as a matrix for preparation to obtain a back pouring solution; the combined action of various components, the transdermal permeability experimental study proves that the accumulated transdermal permeability of 24 hours is up to 53.3 mug/cm ², and the clinical experimental study of the insect repellent effect proves that the insect repellent rate is equivalent to that of a positive control group; the raw materials of the application are natural, the cost is low, the drug resistance and the toxicity residue are avoided, and the breeding production benefit of cattle and sheep can be improved.

Description

Matrine back-watering solution for expelling parasites of cattle and sheep and preparation method and application thereof

Technical Field

The invention relates to the technical field of livestock and poultry pharmaceutical preparations, in particular to matrine back watering solution for expelling parasites of cattle and sheep and a preparation method and application thereof.

Background

Parasitic diseases are one of the important diseases of animals, and seriously harm animal health, hamper the development of animal husbandry and bring great harm to public health. Also in the large-scale breeding process of cattle and sheep, parasite diseases are important diseases which are particularly concerned; common parasitic diseases of cattle and sheep include helminthiasis, mange, sheep rhinomyiasis, cow fly disease and the like, once parasitic infection is encountered, drug treatment or periodic insect expelling is needed as soon as possible, and the use of a back solution for realizing rapid insect expelling is a common insect expelling means in large-scale cultivation.

The back solution is a veterinary preparation for expelling and killing animal parasites, belongs to a transdermal absorption liquid medicine, and is prepared into the transdermal absorption liquid medicine by using pesticide or insect repellent in the using process, special equipment is generally used for expelling and killing external parasites such as cow flies, lice and the like along the back of animals, the existing widely used back solution comprises ivermectin expelling agent, moxidectin expelling agent, levamisole expelling agent and the like, and the back solution has definite curative effect and wide use.

In the prior researches, a plurality of pouring solutions are reported, for example, a stable ivermectin pouring agent is disclosed in the publication No. CN104739753A, and contains ivermectin, a pH buffer agent, an emollient and an oil solvent, and a transdermal administration way is adopted, so that the medicine is slowly released and fully absorbed, the toxic and side effects are reduced, and the effect is definite. The publication No. CN110893239A discloses a phoxim pouring agent, the main components of which comprise phoxim, ivermectin and the like, and the treatment steps are simplified and the treatment effect and the treatment cost performance are improved through the combination of a plurality of antiparasitic drugs. However, the above-mentioned documents mainly use organic phosphates and macrolide chemical components, and toxic side effects are relatively large in the insect repellent process, toxic residues and drug resistance are generated, and the cost of drug administration in large-scale treatment is increased.

In addition, CN104367907a in the prior art discloses a Chinese herbal medicine sheep tick insect repellent, which mainly comprises Chinese herbal medicines such as chinaberry bark, radix stemonae, sweet wormwood herb and the like, and can overcome the problems of toxic residues and drug resistance to a certain extent, but the whole insect repellent effect is poor and the treatment effect is unstable due to the direct extraction of the Chinese herbal medicines.

Matrine is an alkaloid extracted from root, stem and fruit of Sophora flavescens ait of Leguminosae by organic solvent such as ethanol, and has the main functions of clearing heat, eliminating dampness, dispelling pathogenic wind and killing parasite. The insecticidal composition has small side effects on human bodies, but when the insecticidal composition acts on pests, the pests can paralyze nerve centers after contacting, so that the proteins of the pests are solidified, and the air holes of the pests are blocked, thereby realizing the effects of touch killing and stomach toxicity on the pests. The component is natural effective substances, is not artificially synthesized chemical substances, is easy to decompose after the action, has short half-life period and no residue, has little pollution to animals and environment, ensures that parasites are difficult to generate drug resistance, and is a better insect repellent component.

For matrine as an active ingredient of a natural product, the prior art with the publication number of CN1935137A discloses matrine spray for killing sheep body lice, matrine extract is used as an active ingredient, a plurality of auxiliary materials are compounded to prepare the spray, and the spray is applied in a spraying mode, but the spray is used as a natural extract component, has slow effect and has lower curative effect than chemical insect repellents when being sprayed.

Through research and retrieval of the prior art, the prior casting solution mostly takes macrolide chemical components as main components, and toxic residues and drug resistance can be generated; the insect repellent effect of the pouring solution taking natural Chinese herbal medicine components as active components is poor as a whole, and a satisfactory insect repellent effect is difficult to realize; when the matrine which is a traditional Chinese medicine active substance with definite curative effect is utilized, the spray solution is prepared only by adopting a conventional mode, and the problems of slow effect and poor curative effect exist during use.

Aiming at the problems, the matrine back-watering solution for cattle and sheep insect repellent, the preparation method and the application thereof, which take matrine as a main active ingredient and surround the core insect repellent effect, comprehensively improve the application effect when cattle and sheep are back-watering insect repellent through the adjustment of raw material collocation and treatment modes.

Disclosure of Invention

The invention provides matrine back-watering solution for expelling parasites of cattle and sheep, a preparation method and application thereof, aiming at the problems in the prior art, wherein matrine and alliin with definite curative effect are taken as main active components, rice vinegar and menthol are used for promoting permeation, and specific percutaneous absorption raw materials of triolein and ethylene glycol are matched and water is taken as a matrix to prepare the back-watering solution.

In the raw material combination, the specific action mechanism is that alliin accelerates the effect of matrine by promoting vasodilation, rice vinegar has the effect of expelling parasites by providing an acidic environment for matrine, and simultaneously combines menthol to promote the rapid permeation of active ingredients, and menthol has the effect of cooling and relieving itching, so that the discomfort to animals is reduced while expelling parasites; in addition, the glycol is used as an oil-soluble matrix, the triolein is used as an oil-soluble transdermal absorption solution, and the triolein can effectively transport active ingredients to accelerate migration of the active ingredients, and various ingredients act together, so that the prepared back solution is stable and definite in curative effect, and has insect repellent efficacy comparable with that of a chemical pour-on solution.

In order to achieve the above purpose, the present invention firstly provides matrine back-watering solution for expelling parasites of cattle and sheep, wherein the back-watering solution is prepared from active ingredients, penetration promoting ingredients, transdermal auxiliary materials and water; the active ingredients comprise 1-3 parts of matrine and 0.5-1.5 parts of alliin in parts by weight, wherein the mass ratio of matrine to alliin is 2:1, a step of; the permeation promoting component comprises 10-20 parts of rice vinegar and 2-4 parts of menthol; the transdermal auxiliary material comprises 5-10 parts of triolein and 5-10 parts of glycol; 50-80 parts of water.

As a preferable scheme, the matrine for expelling parasites of cattle and sheep is poured into a back solution firstly, and the dosage of each component is calculated according to weight fraction, wherein the composition of the active components is 2 parts of matrine and 1 part of alliin; the permeation promoting component comprises 15 parts of rice vinegar and 3 parts of menthol; the transdermal auxiliary material comprises 8 parts of triolein and 8 parts of glycol; 65 parts of water.

Alliin is taken as unique non-protein sulfur-containing amino acid in garlic, is an active ingredient with outstanding efficacy, and modern researches show that: alliin has various pharmacological effects of lowering blood pressure, resisting bacteria, killing virus, scavenging free radicals, protecting liver, and resisting diabetes.

The rice vinegar is prepared by taking grain crops such as glutinous rice, barley and the like as main raw materials and fermenting and brewing the main raw materials. The rice vinegar can inhibit parasites, and the effect is mainly because the rice vinegar can provide an acidic environment, so that the living environment of the parasites can be destroyed or the parasites can be inactivated, and meanwhile, the rice vinegar is rich in organic acid, so that the transdermal efficiency of the medicine can be improved, and the rapid permeation of active ingredients can be promoted.

Menthol is a traditional Chinese medicine penetration enhancer extracted from peppermint, can bring sterilization and insect repellent effects, and has the effects of cooling and relieving itching when used as skin.

The triolein is a product obtained by polymerization reaction of oleic acid (octadecenoic acid) and glycerol (glycerol), can be used as a transdermal absorption promoter, is a light yellow transparent low-viscosity liquid and is prepared by esterification of oleyl alcohol and high polymer fatty acid mainly comprising oleic acid; the transdermal patch can be used as an oily matrix of a transdermal drug delivery preparation, has excellent skin moisturizing effect, increases the permeation rate of a drug through skin, promotes drug absorption, and particularly can increase the transdermal transmission and migration rate of the drug in oil-based drugs.

Ethylene glycol is a colorless, odorless, sweet, viscous liquid with moisture retention and hygroscopicity, which readily penetrates the skin when contacted therewith as a pharmaceutical adjuvant, promoting interaction.

As a preferable technical scheme, the acidity of the rice vinegar is more than 3.8 g/100 ml.

Since matrine cannot coexist with alkaline substances, the rate can be greatly reduced, and the reaction rate of active ingredients is improved by providing an acidic environment through rice vinegar.

In another aspect of the invention, the invention also provides a preparation method of matrine back solution for expelling parasites of cattle and sheep, which comprises the following preparation steps:

firstly, weighing raw materials according to the weight parts of the raw materials;

Step two, mixing the active ingredient matrine and alliin to obtain an active ingredient mixture, adding rice vinegar into the active ingredient mixture, and fully mixing to obtain an initial mixture;

Step three, adding transdermal auxiliary materials of triolein and ethylene glycol into menthol, and stirring and mixing to obtain a secondary mixture;

stirring and mixing the initial mixture, the secondary mixture and water to obtain a final mixture;

And fifthly, sterilizing the final mixture and packaging to obtain matrine back solution.

As a preferable technical scheme, the stirring and mixing rotating speed in the fourth step is 200-600rpm, and the mixing time is 4-8 minutes.

Further, the sterilization mode in the fifth step is one of pasteurization, ultra-high temperature instantaneous sterilization or ultra-high pressure sterilization.

The third aspect of the invention also provides an application of matrine back solution for expelling parasites of cattle and sheep in preparing cattle and sheep insect repellent medicines; the back-watering solution is used for back-watering on the backs of cattle and sheep in the using process, and the dosage is 0.5-3ml/10kg.

The technical scheme of the invention has the following beneficial effects:

(1) According to the technical scheme, matrine back solution is provided, and the effectiveness of the active ingredients is improved, the drug mobility is accelerated, and the efficacy of the active ingredients can be fully volatilized finally, so that the overall curative effect is comparable to that of chemical back solution.

(2) In the aspect of the efficacy exertion of active ingredients, matrine is taken as a core active ingredient to exert the main effect of expelling parasites, but matrine is taken as a natural extract active ingredient to have the defect of slow effect compared with chemical medicines, and after the matrine is selected to be matched with alliin, the alliin has the capability of inhibiting biological growth and killing microorganisms, and especially can promote vasodilation and accelerate blood circulation, so that the characteristic of promoting the vasodilation and accelerating the blood circulation by utilizing the alliin can accelerate the active ingredient to act and synergistically promote the insect expelling effect of matrine;

According to the invention, rice vinegar and menthol are further selected to be compounded as permeation promoting components, and as permeation is the premise of transdermal absorption, effective permeation can promote the redistribution and diffusion of the effective components, and a good basis is provided for absorption, the rice vinegar provides an acidic environment for permeation, the menthol can reduce the barrier of a stratum corneum, change the ultrastructure of skin epidermis, effectively promote the permeation of matrine to various parts of skin, and meanwhile, the matrine has the effects of cooling and relieving itching, and can reduce discomfort caused by parasites to the skin;

According to the scheme, the triolein and the ethylene glycol belong to raw materials for percutaneous absorption, so that the lipophilic triolein can accelerate migration of active ingredients, promote percutaneous absorption, and reach deep layers of skin to effectively exert efficacy; experiments prove that the triolein has excellent transdermal absorption effect compared with other transdermal absorption preparations, and the triolein can lead the insect repellent effect of the active ingredient to be better after being compounded with ethylene glycol.

(3) The components of the invention act together, and the prepared back solution is stable and has definite curative effect; the cattle and sheep are taken as experimental objects, the transdermal permeability experimental study proves that the accumulated transdermal permeability of 24 hours is up to 53.3 mug/cm ², which can be comparable with that of a positive control group, and the clinical experimental study of the insect repellent effect proves that the embodiment group of the invention can achieve 100% of insect repellent rate, is obviously higher than that of a control group and is comparable with that of the positive control group; the cattle and sheep back solution has good industrial application effect, natural raw material selection, low cost, no drug resistance and no toxicity residue, and can improve the cattle and sheep breeding production benefit.

Detailed Description

Other advantages and effects of the present invention will be readily apparent to those skilled in the art from the following disclosure of the present invention, by referring to the following specific embodiments; it will be apparent that the described embodiments are only some, but not all, embodiments of the invention; the invention may be practiced or carried out in other embodiments that depart from the specific details, and the details of the present description may be modified or varied from the spirit and scope of the present invention.

It should be noted that, without conflict, the following embodiments and features in the embodiments may be combined with each other; all other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

The main raw materials of the invention are as follows:

matrine was purchased from the company limited for the development of the technology of the science of the western security;

alliin was purchased from Shanghai Seiyaka Biotechnology Co., ltd;

the rice vinegar is classic rice vinegar;

menthol was purchased from Shanghai Ala Biochemical technologies Co., ltd;

triolein was purchased from Shanghai Ala Biochemical technologies Co., ltd;

Ethylene glycol was purchased from sigma aldrich (Shanghai) trade limited.

Example 1

Matrine back-watering solution for expelling parasites of cattle and sheep, wherein the back-watering solution is prepared from active ingredients, penetration promoting ingredients, transdermal auxiliary materials and water; the active ingredients comprise 2 parts of matrine and 1 part of alliin according to parts by weight; the permeation promoting component comprises 15 parts of rice vinegar and 3 parts of menthol; the transdermal auxiliary material comprises 8 parts of triolein and 8 parts of glycol; 65 parts of water;

The preparation method comprises the following steps:

firstly, weighing raw materials according to the weight parts of the raw materials;

Step two, mixing the active ingredient matrine and alliin to obtain an active ingredient mixture, adding rice vinegar into the active ingredient mixture, and fully mixing to obtain an initial mixture;

step three, adding transdermal auxiliary materials of triolein and ethylene glycol into menthol, stirring and mixing, wherein the stirring and mixing speed is 400rpm, and the mixing time is 6 minutes, so as to obtain a secondary mixture;

stirring and mixing the initial mixture, the secondary mixture and water to obtain a final mixture;

And fifthly, packaging the final mixture after ultrahigh temperature instantaneous sterilization to obtain matrine back solution.

Example 2

Matrine back-watering solution for expelling parasites of cattle and sheep, wherein the back-watering solution is prepared from active ingredients, penetration promoting ingredients, transdermal auxiliary materials and water; the active ingredients comprise 1 part by weight of matrine and 0.5 part by weight of alliin; the permeation promoting component comprises 10 parts of rice vinegar and 2 parts of menthol; the transdermal auxiliary material comprises 5 parts of triolein and 5 parts of glycol; 50 parts of water;

The preparation method comprises the following steps:

firstly, weighing raw materials according to the weight parts of the raw materials;

Step two, mixing the active ingredient matrine and alliin to obtain an active ingredient mixture, adding rice vinegar into the active ingredient mixture, and fully mixing to obtain an initial mixture;

step three, adding transdermal auxiliary materials of triolein and ethylene glycol into menthol, stirring and mixing, wherein the stirring and mixing speed is 200rpm, and the mixing time is 4 minutes, so as to obtain a secondary mixture;

stirring and mixing the initial mixture, the secondary mixture and water to obtain a final mixture;

And fifthly, packaging the final mixture after ultrahigh temperature instantaneous sterilization to obtain matrine back solution.

Example 3

Matrine back-watering solution for expelling parasites of cattle and sheep, wherein the back-watering solution is prepared from active ingredients, penetration promoting ingredients, transdermal auxiliary materials and water; the active ingredients comprise 3 parts of matrine and 1.5 parts of alliin according to parts by weight; the permeation promoting component comprises 20 parts of rice vinegar and 4 parts of menthol; the transdermal auxiliary material comprises 10 parts of triolein and 10 parts of glycol; 80 parts of water;

The preparation method comprises the following steps:

firstly, weighing raw materials according to the weight parts of the raw materials;

Step two, mixing the active ingredient matrine and alliin to obtain an active ingredient mixture, adding rice vinegar into the active ingredient mixture, and fully mixing to obtain an initial mixture;

Step three, adding transdermal auxiliary materials of triolein and ethylene glycol into menthol, stirring and mixing, wherein the stirring and mixing speed is 600rpm, and the mixing time is 8 minutes, so as to obtain a secondary mixture;

stirring and mixing the initial mixture, the secondary mixture and water to obtain a final mixture;

And fifthly, packaging the final mixture after ultrahigh temperature instantaneous sterilization to obtain matrine back solution.

Comparative example

Comparative example 1 selection of active ingredients

Compared with example 1, the difference is only that alliin is replaced by equal amount of matrine, i.e. 3 parts of matrine is used as active ingredient, and the rest is the same as example 1.

Comparative example 2 selection of active ingredients

Compared with example 1, the difference is only that the dosage ratio of matrine and alliin is different, 1 part of matrine and 2 parts of alliin are selected, namely the dosage ratio is 1:2, the remainder being the same as in example 1.

Comparative example 3 selection of active ingredients

Compared with example 1, the difference is only that the dosage ratio of matrine and alliin is different, 1.5 parts of matrine and 1.5 parts of alliin are selected, namely the dosage ratio is 1:1 and the rest are the same as in example 1.

Comparative example 4 selection of penetration enhancing component

The difference compared with example 1 is that menthol is replaced with an equal amount of rice vinegar, i.e., the permeation promoting component has a composition of 18 parts of rice vinegar, and the rest is the same as in example 1.

Comparative example 5 selection of transdermal adjuvant

The difference compared to example 1 is only that the triolein is replaced by an equivalent amount of eucalyptus oil, the remainder being the same as in example 1.

Comparative example 6 selection of transdermal adjuvant

The only difference compared to example 1 is that the triolein is replaced by an equal amount of isopropyl palmitate, the remainder being the same as in example 1.

Positive control group: as a control, a commercially available ivermectin transdermal pour-on solution was used.

The brand of the commercially available ivermectin transdermal pouring solution is DAZNO, and the trade name of the commercially available ivermectin transdermal pouring solution is called as 'Dazhongnong'.

Experimental example 1 transdermal penetration experiment study

The experimental method comprises the following steps: the transdermal permeability results of each experimental group and control group were measured according to a conventional method in the art by using RYJ-12B type drug transdermal diffusion tester, using 30% ethanol physiological saline solution as a receiving solution, using the abdominal skin of the mice as a study object, and by adding the receiving solution and sandwiching the abdominal skin of the mice between the two chambers during experimental study. The measurement results are specifically shown in Table 1.

TABLE 1 results of the transdermal permeability experiments for different groups

As shown in Table 1, the results of the scalp permeability experiments of different experimental groups and control groups are shown in Table 1, it is clear that the accumulated transdermal permeability data of each experimental group measured in different time periods is obviously due to the control group and is equivalent to that of the positive control group, and from different test time periods, the absorption effect of the experimental example of the invention is quick, the experimental example can permeate rapidly in a short time, especially 6 hours before the application, and the accumulated permeability data in 24 hours are better than those of other control groups, mainly because of the addition of alliin in the active ingredients of the invention, the reasonable selection of permeation promoting components and the targeted selection of transdermal absorption auxiliary materials; in conclusion, the research results in table 1 can show that under the compatibility of the raw materials and the auxiliary materials, the transdermal absorption performance of the product is better, which lays a good foundation for clinical experiments of essential medicines.

Experimental example 2 clinical trial study of the insect repellent effect of the dorsal solution

The research method comprises the following steps: checking the back of a cow in a large farm by palpation, confirming whether the cow is infected with cow fly maggots according to the outline of the tumor bulls on the back of the cow, further screening out cow infected with cow fly maggots as test samples, screening 220 heads altogether, randomly dividing the cow into 11 groups (wherein the test group 3, the control group 6, the positive control group 1 and the blank control group 1), and 20 heads in each group; after taking a test animal cow as a sample, sucking the medicine by using a needleless injector, and then pouring and administering along the back central line of the cow, wherein a blank control group does not carry out any treatment, and the administration amount is poured and administered according to the standard of 1ml of medicine liquid administered per 10kg of body weight; and (3) continuously feeding 7d, after 1 month of the feeding end interval, respectively checking whether tumor blisters or wormholes exist on the backs of the experimental group and the control group, and faithfully recording the specific conditions of each cattle, and determining the control effect according to the same standard.

Drive rate = (trial Niu Toushu-number of incurable cattle after dosing)/number of experimental cattle x 100%

Insect repellent rate= (number of control group tumor blisters-number of test group tumor blisters)/number of control group tumor blisters x 100%

TABLE 2 clinical trial study of the insect repellent effect of different groups of dorsal solution

Through experimental study, the number of tumor blisters of the blank control group is 78, the expelling rate and the expelling rate calculated according to the formula are shown in table 2, and from the table, it is not difficult to clearly determine that the experiment group and the positive control group can almost realize 100% expelling cleanliness, and therefore, the expelling rate of the embodiment is close to that of the positive control group. From the point of more specific insect repellent rate, the effect of the example group is significantly better than that of each comparative example, and there is a significant difference between the insect repellent rate of the comparative example and the example group, such as that in comparative example 1, the insect repellent rate is reduced to 91% after alliin is replaced, but the effect is also reduced after the proportion of the active ingredient is adjusted, and the result of comparative example 4 after menthol is replaced shows that the reduction of both the insect repellent rate and the insect repellent rate is obvious; in addition, the effect after the transdermal auxiliary materials are replaced is obviously inferior to that of the embodiment 1. The results can prove that the back solution has better insect expelling effect compared with different comparative examples and is equivalent to the commercial positive control group.

The foregoing is merely illustrative of the present invention, and the present invention is not limited thereto, and any changes or substitutions easily contemplated by those skilled in the art within the scope of the present invention should be included in the present invention.

Claims (6)

1. Matrine back-watering solution for expelling parasites of cattle and sheep is characterized by being prepared from active ingredients, penetration promoting ingredients, transdermal auxiliary materials and water; the active ingredients comprise 1-3 parts of matrine and 0.5-1.5 parts of alliin in parts by weight, wherein the mass ratio of matrine to alliin is 2:1, a step of; the permeation promoting component comprises 10-20 parts of rice vinegar and 2-4 parts of menthol; the transdermal auxiliary material comprises 5-10 parts of triolein and 5-10 parts of glycol; 50-80 parts of water;

The acidity of the rice vinegar is more than 3.8 g/100 ml;

The matrine back solution comprises the following preparation steps:

firstly, weighing raw materials according to the weight parts of the raw materials;

Step two, mixing the active ingredient matrine and alliin to obtain an active ingredient mixture, adding rice vinegar into the active ingredient mixture, and fully mixing to obtain an initial mixture;

Step three, adding transdermal auxiliary materials of triolein and ethylene glycol into menthol, and stirring and mixing to obtain a secondary mixture;

stirring and mixing the initial mixture, the secondary mixture and water to obtain a final mixture;

And fifthly, sterilizing the final mixture and packaging to obtain matrine back solution.

2. The matrine casting back solution for expelling parasites from cattle and sheep as claimed in claim 1, wherein each component is used in an amount by weight, wherein the composition of the active components is matrine 2 parts and alliin 1 part; the permeation promoting component comprises 15 parts of rice vinegar and 3 parts of menthol; the transdermal auxiliary material comprises 8 parts of triolein and 8 parts of glycol; 65 parts of water.

3. The matrine back solution for insect repellent of cattle and sheep according to claim 2, wherein the stirring and mixing speed in the fourth step is 200-600rpm, and the mixing time is 4-8 minutes.

4. The matrine casting back solution for insect repellent of cattle and sheep according to claim 2, wherein the sterilization mode in the fifth step is one of pasteurization, ultra-high temperature instantaneous sterilization or ultra-high pressure sterilization.

5. Use of matrine casting solution for insect repellent of cattle and sheep according to any one of claims 1-2 for preparing insect repellent drug of cattle and sheep; the medicine is a medicine for expelling the maggots of the cow leather.

6. The use according to claim 5, wherein the topping solution is applied to the back of cattle and sheep during use in an amount of 0.5-3ml/10kg.