CN112843093B - Cat immune factor oral liquid and application thereof - Google Patents
Cat immune factor oral liquid and application thereof Download PDFInfo
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- CN112843093B CN112843093B CN202110149774.0A CN202110149774A CN112843093B CN 112843093 B CN112843093 B CN 112843093B CN 202110149774 A CN202110149774 A CN 202110149774A CN 112843093 B CN112843093 B CN 112843093B
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- oral liquid
- immune factor
- cat
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- water
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Abstract
The application discloses a cat immune factor oral liquid, which contains 10-30% of transfer factor, 1-5% of astragalus polysaccharide, 1-10% of sweetener, 0.5-5% of sodium chloride and water for injection. The application also discloses a preparation method and specific application of the cat immune factor oral liquid, and the cat immune factor oral liquid has the characteristics of small dosage and good curative effect, and is applied to preparing medicines widely used in the clinic of pets.
Description
Technical Field
The application relates to an oral preparation and a preparation method thereof, in particular to an oral preparation with an immunity enhancing function and a preparation method thereof.
Background
With the increasing standard of living of people, home pet feeding is gradually becoming popular. However, many infectious diseases of pets have zoonotic property, and cause little harm to the development of pet property and the health of human beings. Therefore, it is imperative to improve the immunity of the pets and ensure the healthy growth of the pets.
The transfer factor is a mixture of small molecule active substances such as polypeptide, amino acid, ribose and the like extracted from animal spleen, and is a cell immunity promoter. Can make animal body quickly obtain specific and nonspecific cell immunity function, and can promote the generation and release of interferon and tumor necrosis factor. The transfer factor carries specific immunity information of sensitized lymphocytes, can present the specific immunity information to receptor lymphocytes, and enables the receptor inactive lymphocytes to be converted into the specific sensitized lymphocytes, so that immune response mediated by the receptor cells is stimulated. The immune factor has wide immunoregulatory activity, can induce immune cell activation on one hand, and can enhance the nonspecific immunity of organisms; on the other hand, the specific immune information can be transmitted to the recipient animal, and the animal is stimulated to generate specific immune response. The immune factor is a small molecular active substance, can not be decomposed by pepsin and trypsin, can not be damaged by gastric acid, can be orally taken, has no species specificity, no toxic or side effect and no antigenicity, and can enable the organism to generate local or systemic immune response by using the dosage as small as 0.01 unit. The effect is quick, and lymphocytes of the recipient animal can be activated within 4 hours at maximum, so that the recipient is sensitized; the effect lasts for a long time, and can last for months to one year.
Cats can be bred on a large scale as common companion animals, but common viruses infect places with high population densities in houses, such as houses, farms, cat houses and multi-cat feeding areas. Cats can only develop a state of virulence, intermittently expelling toxins, especially in cases of stress, hypoimmunity or immunosuppressive therapy where detoxification is activated. Delivery and lactation can cause the latent infection to be reactivated, which can subsequently infect kittens and non-vaccinated adult cats. Therefore, the improvement of the immunity of the cats has extremely important effects on the feeding and breeding of the cats.
In the prior art, immune factor oral liquid added with traditional Chinese medicines is available, but traditional Chinese medicines such as ginseng, ganoderma lucidum, rhodiola rosea and the like which are used for thousands of years are widely used. Most of the biological and chemical preparation medicines have stronger toxic and side effects; while traditional medicinal materials such as ginseng, ganoderma lucidum, rhodiola rosea and the like with the immunity enhancing function have small toxic and side effects, the traditional medicinal materials can play an obvious role in immunity enhancing after being taken for a long time, and the traditional medicinal materials are high in price, so that the traditional medicinal materials far exceed the payment capability of common families. Meanwhile, these drugs are commonly used in humans, and have limited effects on animals, particularly companion animals such as cats and dogs, and few specific applications are available, particularly in view of cost. And because of the characteristics of companion animals such as cats, dogs and the like, a targeted immune oral is more needed.
Meanwhile, the stability of the oral liquid is extremely important, and the problem of the prior art is generally solved by adopting a mode of adding an adhesive matrix, such as pectin and/or alginate, a thickening agent, a stabilizing agent and the like. Although the compositions described in these prior arts have an effect of increasing stability to some extent, when the oral liquid compositions are prepared by blending the raw materials described in these patents, there is a problem that aggregates are generated during preparation and/or storage, so that the related compositions in the prior arts are mostly gel-like, and on the one hand, a large amount of other components need to be added to maintain their jelly-like state, and at the same time, a large amount of other components added thereto cause immune reaction of the animal body, causing fever, vomiting, anxiety, dysphoria, etc. of the animal body, changing the life habits and states of companion animals, and sometimes causing the animal biting other animals, owners or other personnel, which seriously affects the practical use effect of the drugs. On the other hand, the composition has poor stability and short storage period, and no related technical means can conveniently and quickly solve the problem. Further, if such aggregates are generated, when the prepared composition is taken through a tube, there is a problem that clogging of the tube occurs due to the aggregates existing in the oral liquid composition (particularly clogging of aggregates occurs in the portion of the speed adjusting throttle valve that adjusts the administration speed). Further, the viscosity of the liquid oral liquid composition increases due to the presence of aggregates, and thus the hose passing property of the liquid oral liquid composition also deteriorates. Further, when the prepared composition is taken orally, the "non-slippery feeling" is large due to the presence of aggregates, and the "feeling upon ingestion" is extremely poor due to the high viscosity caused by the presence of aggregates, resulting in increased discomfort for the pet, and it is difficult to administer the composition for a long period of time or a large number of times.
Disclosure of Invention
In order to solve the problems, the application provides a cat immune factor oral liquid, which comprises, by weight, transfer factors (final concentration of 1-10 mg/ml), 1-5% of astragalus polysaccharide, 1-10% of sucrose, 0.5-5% of sodium chloride, 0.1-1% of potassium sorbate, 0.1-1.0% of taurine and water for injection.
Furthermore, the cat immune factor oral liquid has p H value of 6.4-7.4, good solubility and no stimulation to animals.
Further, the cat immune factor oral liquid of the present application is excellent in fluidity and stability, and preferably has a viscosity of 300cP or less, more preferably 150cP or less, still more preferably 100cP or less, and particularly preferably 50cP or less in terms of 1wt% aqueous solution (20 ℃).
Further, the particle size distribution of the oral liquid is multimodal, preferably bimodal, preferably, the oral liquid has at least 1 peak at a particle size of 2000nm or less, more preferably 1000nm or less, still more preferably 500nm or less.
Further, the frequency of the 1 st peak with smaller particle size is higher than that of the 2 nd peak with larger particle size in the bimodal distribution diagram;
further, the oral liquid was in a uniform liquid state, the viscosity at 30 ℃ was 150cP or less, and the oral liquid was kept at rest for one year at room temperature, and the pH and viscosity were hardly changed, and no visible aggregates were found.
Further, the application provides a preparation method of the cat immune factor oral liquid, which comprises the following steps:
1. transfer factor preparation
(1) Cutting and picking: the thawed and melted canine spleen is removed and bagged, strictly selected according to the appearance requirements in the raw material standard, and the fat is clamped by forceps and sheared by scissors.
(2) Cleaning: accurately weighing the feeding amount of the sheared raw materials, cleaning the weighed raw materials with 0.8% NaCl solution for 2-3 times, and draining.
(3) Primary twisting: the raw materials are placed in a charging hopper of a meat grinder, the operation is carried out according to the operation rules of the meat grinder, the raw materials are primarily ground for 1 time, and the raw materials are contained in a clean material barrel.
(4) Finish twisting: mixing the raw materials after primary twisting with water for injection according to the proportion of 1:1.5, placing into a charging hopper, grinding for 4 times according to the operation procedure of a colloid mill, preparing homogenate, adjusting pH to 4.8 with 2mol/L HCl, placing into a saline bottle or a plastic bottle, repeatedly freezing and thawing for 6 times at-20 ℃, and quickly thawing (or naturally thawing at the temperature lower than 37 ℃) with running water.
(5) And (3) centrifugal separation: centrifuging the freeze-thawed homogenate with a refrigerated centrifuge at 8000rpm at 4deg.C for 30min, discarding the precipitate, collecting supernatant, adjusting pH to 6.8 with 2mol/L NaOH, and prefiltering or freeze-preserving at-20deg.C.
(6) Prefiltering: the supernatant after centrifugation was subjected to 1um straining and then ultrafiltration with a 300KD prefilter column having a molecular weight cut-off to obtain a clear filtrate.
(7) Ultrafiltration: ultrafiltering the filtrate with ultrafiltration membrane with molecular weight cutoff of 10KD-0.5KD, collecting active polypeptide refined solution, quantifying, and storing.
2. Precisely weighing radix astragali polysaccharide powder according to weight ratio, adding appropriate amount of water for injection, stirring to dissolve completely, and performing primary filtration with 0.45um microporous filter.
3. Transferring the astragalus polysaccharide solution into a liquid preparation tank, sequentially adding sucrose, potassium sorbate, sodium chloride, taurine and transfer factors prepared in the steps, and stirring until the components are completely dissolved.
4. Adding water for injection to the corresponding volume, stirring for 10-20 minutes, and adjusting the pH value to 6.4-7.4 by using hydrochloric acid or sodium hydroxide.
5. The solution obtained was treated with ultrasound. The method comprises the following steps: firstly, cooling the solution to 0-4 ℃ at a speed of 2-5 ℃/h, firstly treating for 15s at 2KW and 1KHz, and repeating for 3-5 times at a gap of 10 s; treating with 3KW and 2KHz for 15s, and repeating for 3-5 times at a gap of 10 s; treating with 4KW and 2KHz for 10s, and repeating for 3-5 times at 10 s; finally, the mixture is treated for 15s with 4KW and 3KHz, the gap is 10s, and the mixture is repeated for 3 to 5 times. After incubation for 1h at 0-4℃the temperature was returned to room temperature at a rate of 2-5℃per hour.
6. Sterilizing and filtering the medicinal liquid with 0.22um microporous filter, and packaging for storage.
Wherein the astragalus polysaccharide is water-soluble heteropolysaccharide obtained by extracting, concentrating and purifying dried root of Astragalus mongholicus bge or Astragalus membranaceus bge. The astragalus polysaccharide is composed of hexuronic acid, glucose, fructose, rhamnose, arabinose, galacturonic acid, glucuronic acid and the like, can be used as an immunity promoter or regulator, and has the effects of resisting virus, tumor, aging, radiation, stress, oxidization and the like. The astragalus polysaccharide can induce organism to produce interferon, interfere the replication of virus in the organism, improve the immune function of the organism, promote the enhancement of the activity of superoxide dismutase and glutathione peroxidase; can strengthen and stimulate the generation of lymphocyte and reticuloendothelial layer cell, strengthen the phagocytic function of reticuloendothelial layer cell and macrophage, and has good promoting and regulating effects on humoral, mucous membrane and cellular immunity.
Potassium sorbate is one of the few preservatives permitted by the world health organization additives committee, has high safety and strong mold inhibition capacity, has three advantages of corrosion resistance, safety and stability, is regulated as a "recognized safety" (class) variety by the U.S. food and drug administration, and is commonly used abroad. The potassium sorbate inhibits the growth of microorganisms by inhibiting a dehydrogenase system in the microorganisms, so that the aim of corrosion prevention is fulfilled, and the potassium sorbate has inhibition effect on bacteria, mold and saccharomycetes.
Sucrose is mainly used for improving the taste of oral liquid and increasing the palatability of the oral liquid.
Sodium chloride is an isotonic regulator, so that the obtained oral liquid is isotonic, the osmotic pressure ratio is about 0.9-1.1, the product has similar osmotic pressure with body fluid, the irritation of clinical use is reduced, the palatability is improved, and the irritation caused by the stomach intestine of a cat is avoided.
The pH value of the oral liquid is 6.4-7.4 by using hydrochloric acid or sodium hydroxide pH regulator, which is similar to the pH value of body fluid, so that the safety and comfort of use are improved, and the irritation is small.
Taurine is an important essential amino acid for cats, and has important functions in maintaining eyesight, guaranteeing immunity of heart and organism, and reproducing functions.
Advantageous effects
The product is a high-efficiency immunopotentiator, and has effects of resisting infection, stress, tumor and vaccine. The product is used for the adjuvant treatment of viral diseases such as cat fineness, cat nasal branch, cat leukemia, cat pneumonia, etc. The immune factors are orally taken during vaccination, so that the time for generating the antibody can be shortened, the antibody titer can be improved, and the effect of vaccine synergism can be achieved. Improving immunity and anti-stress capability of cat, and can be used for preventing and treating immunodeficiency of cat, and immunosuppression caused by stress, medicine, and operation. Activating lymphocyte, promoting generation and release of tumor necrosis factor, enhancing phagocytic function of organism immunocyte on tumor cell, and resisting tumor.
The oral liquid has stable structure, can be durable and stable within 12 months, is clear and transparent, does not generate newly added impurities, and is safe, effective and controllable in quality.
Drawings
In the graph of fig. 1, the horizontal axis represents the average particle diameter, the vertical axis represents the distribution frequency of the particle diameter, and the peak in the particle diameter distribution represents the point of the maximum frequency value in the distribution curve of the mountain shape with the horizontal axis (particle diameter) as the bottom, wherein a to f correspond to examples 1 and comparative examples 1 to 5, respectively.
Figure 2 is a character picture of part of cat immune factor oral liquid, wherein A is colorless transparent liquid, and figure B is yellowing liquid after 6 months.
FIG. 3 shows the results of a pass test of hose feeding.
Fig. 4 is a clinical picture of cat only, wherein fig. a is a clinical picture of eyes before illness and fig. B is a clinical picture of eyes after cure.
Detailed Description
The following examples further illustrate the application but are not to be construed as limiting the application. Modifications and substitutions to methods, procedures, or conditions of the present application without departing from the spirit and nature of the application are intended to be within the scope of the present application.
The technical means used in the examples are conventional means well known to those skilled in the art unless otherwise indicated.
Example 1. A method for preparing oral liquid of cat immune factor,
taking 10000ml cat immune factor oral liquid as an example, the steps are as follows.
1. Transfer factor preparation
(1) Cutting and picking: the thawed and melted canine spleen is removed and bagged, strictly selected according to the appearance requirements in the raw material standard, and the fat is clamped by forceps and sheared by scissors.
(2) Cleaning: accurately weighing the feeding amount of the sheared raw materials, cleaning the weighed raw materials with 0.8% NaCl solution for 2-3 times, and draining.
(3) Primary twisting: the raw materials are placed in a charging hopper of a meat grinder, the operation is carried out according to the operation rules of the meat grinder, the raw materials are primarily ground for 1 time, and the raw materials are contained in a clean material barrel.
(4) Finish twisting: mixing the raw materials after primary twisting with water for injection according to the proportion of 1:1.5, placing into a charging hopper, grinding for 4 times according to the operation procedure of a colloid mill, preparing homogenate, adjusting pH to 4.8 with 2mol/L HCl, placing into a saline bottle or a plastic bottle, repeatedly freezing and thawing for 6 times at-20 ℃, and quickly thawing (or naturally thawing at the temperature lower than 37 ℃) with running water.
(5) And (3) centrifugal separation: centrifuging the freeze-thawed homogenate with a refrigerated centrifuge at 8000rpm at 4deg.C for 30min, discarding the precipitate, collecting supernatant, adjusting pH to 6.8 with 2mol/L NaOH, and prefiltering or freeze-preserving at-20deg.C.
(6) Prefiltering: the supernatant after centrifugation was subjected to 1um straining and then ultrafiltration with a 300KD prefilter column having a molecular weight cut-off to obtain a clear filtrate.
(7) Ultrafiltration: ultrafiltering the filtrate with ultrafiltration membrane with molecular weight cutoff of 10KD-0.5KD, collecting active polypeptide refined solution, quantifying, and storing.
2. 200g of astragalus polyose powder is precisely weighed, 4000ml of water for injection is added, the mixture is stirred until the water is completely dissolved, and a microporous filter with 0.45um is used for primary filtration.
3. Transferring the astragalus polysaccharide solution into a liquid preparation tank, sequentially adding 100g of sucrose, 10g of potassium sorbate, 50g of sodium chloride, 10g of taurine and transfer factors (ensuring the final concentration is 8 mg/ml), and stirring until the solution is completely dissolved.
4. Adding water for injection to 10000ml, stirring for 10-20 min, and regulating pH value to 6.4-7.4 by using hydrochloric acid or sodium hydroxide.
5. The solution obtained was treated with ultrasound. The method comprises the following steps: firstly, treating for 15s with 2KW and 1KHz, and repeating for 3-5 times with a gap of 10 s; treating with 3KW and 2KHz for 15s, and repeating for 3-5 times at a gap of 10 s; treating with 4KW and 2KHz for 10s, and repeating for 3-5 times at 10 s; finally, the mixture is treated for 15s with 4KW and 3KHz, the gap is 10s, and the mixture is repeated for 3 to 5 times. After incubation for 1h at 0-4℃the temperature was returned to room temperature at a rate of 2-5℃per hour.
6. Sterilizing and filtering the medicinal liquid with 0.22um microporous filter, and packaging for storage.
Comparative examples 1 to 5
In order to verify the stability of the oral liquid and the interrelationship between the ingredients and specific operating parameters in example 1, comparative examples were set for key steps thereof, specifically:
comparative examples 1 and 2 were prepared in the same manner as in example 1, but without transfer factor and astragalus polysaccharide, respectively;
comparative example 3 was prepared as in example 1, but without the sonication stage;
comparative example 4 the preparation was the same as in example 1, except that the parameters of the sonication stage were: firstly, the temperature of the solution is reduced to 0-4 ℃ at the speed of 3-10 ℃/h, the solution is treated for 30s at the speed of 4KW and 1KHz, the gap is 30s, and the process is repeated for 10-15 times. After incubation for 1h at 0-4℃the temperature was returned to room temperature at a rate of 3-10℃per hour.
Comparative example 5 the preparation was the same as example 1, but with the ultrasound procedure being carried out at room temperature.
Example 2 particle size distribution detection of cat immune factor oral
In this example, the particle size distribution of particles of the oral liquid was measured and evaluated by using a particle size distribution measuring apparatus or the like using a laser diffraction/scattering method. The particle size distribution measuring apparatus was a laser diffraction/scattering type particle size distribution measuring apparatus (Horiba laser diffraction/scattering type particle size distribution measuring apparatus LA-350 in france).
The measurement conditions using the laser diffraction/scattering type particle size distribution measuring apparatus were as follows: dispersion medium: distilled water, refractive index of sample: 1.600 to 0.000i, refractive index of the dispersion medium: 1.333, circulation speed: 13. stirring speed: the sample concentration is adjusted so that the light transmittance (R) reaches 90 to 80% and the transmittance (B) reaches 90 to 70% at the time of measurement. The particle size distribution of the particles was measured under the above-mentioned measurement conditions.
The particle size distribution (as shown in FIG. 1) of the liquids of example 1 and comparative examples 1 to 5 was measured, wherein the particle size distribution of the particles was represented by a distribution curve of the frequency (%) with the horizontal axis as the particle diameter (nm) and the vertical axis as the volume basis. It can be seen from the figure that the liquid composition obtained in example 1 of the present application was changed from a single unimodal distribution to a bimodal distribution after ultrasonic treatment, one of which was located below 500nm in particle size. It is also apparent from the analysis that, in particular, the oral liquid composition having 2 or more peaks in the particle size distribution tends to suppress the occurrence of aggregates, that is, to improve the stability. It was found that the above-mentioned oral liquid composition having a specific change in particle distribution characteristics can be obtained by ultrasonic treatment.
From the above results, it was found that the occurrence of aggregates was related to the change in particle size distribution. The method comprises the following steps: the oral liquid composition of the present application is a particle system, and the particle system consists of particles with different sizes, and thus belongs to a polydisperse system. The particle size distribution refers to the distribution rule of the particle sizes of all particles in the composition particle system. The particle size distribution of the actual population of particles is strictly discontinuous, but can be considered continuous when the number of measurements is large. The water-soluble dietary fiber contained in astragalus polysaccharides is generally poor in suitability for particles (macromolecules such as oils and proteins contained in transfer factors) in the composition, and aggregation of the particles is induced by various actions such as evacuation interaction, electrostatic interaction, intermolecular crosslinking, and the like. In the process of generating "aggregation", there is a stage in which particles in the composition are aggregated as a preceding stage thereof, and then "aggregation" is generated when the "aggregated" particles are combined. That is, particles in the "aggregated" state are easily redispersed each other because the particles each remain independent, but particles in the "agglomerated" state are not redispersed each other because the particles each bind. It is further believed that the particles in the "agglomerated" state "aggregate with each other and further agglomerate to form larger agglomerates, thereby forming a vicious circle. The application realizes two or more aggregation states of particles with different particle diameters through specific ultrasonic treatment, so that the particles exist in a dispersion system in an aggregation state to a certain extent, rather than forming a uniform aggregation state, thereby fundamentally solving the technical problems of unstable dispersion system and easy aggregation.
And it can be seen from the comparison between before and after ultrasonic treatment that the frequency of the 1 st peak on the left side (particle diameter less than 500 nm) is higher than the frequency of the 2 nd peak on the right side (particle diameter about 10000 nm) after further ultrasonic dispersion. This is because the particles constituting the 2 nd peak are many smaller particles and aggregates of aggregates. Since such a set may be continuously dispersed and each particle remains independent, redispersion can be easily performed by a load of an external force such as ultrasonic waves (see comparison of fig. 1a and 1 f). Moreover, the existence of the aggregate does not totally disappear due to ultrasonic treatment, but the specific particle size distribution characteristic is presented, so that a better stabilizing effect is realized.
Example 3 stability detection of oral liquid of cat immune factor
The stability test was performed on 6 products in total of the products of example 1 and comparative examples 1 to 5. The above products were subjected to accelerated tests at a temperature of 40.+ -. 2 ℃ in a constant temperature and humidity incubator and a relative humidity of 75.+ -. 5% (saturated sodium chloride solution), and were sampled at the end of month 3, 6 and 12 (pictures see FIG. 2), and mass detection of the relevant substances, microorganisms, traits and major microorganisms was carried out by the method of BP2005 (see Table 1) according to the items in the following table.
Table 1 stability test of the products
The stability test results show that: the product of example 1 was acceptable in both content and purity after 12 months of standing under accelerated conditions, and no major microorganisms were detected, and the stability of the liquid was significantly higher than that of other products. The content and purity of the partial comparison product are qualified in 3 months, but the appearance and purity of the partial comparison product after being placed for 6 months are obviously beyond the qualified range of ICH to general preparation products, obvious turbidity or layering phenomenon exists after 12 months, the partial comparison product cannot be used normally, and in general, the stability acceleration result in 6 months is stable, so that the effective period of the product can be as long as 3 years, and the quality of the cat immune factor oral liquid is obviously superior to that of the comparison product.
Further, the passing property of feeding via a tube (hose) was tested by using the oral liquids in example 1 and comparative examples 1 to 5.
The hose used in the test was a universal hose for pet feeding having a throttle valve for speed adjustment at a position of about 16Fr thick and 135cm long and 30cm from the end of one side of the hose. In the test, the oral liquid is transferred into the plastic bottle, the oral liquid is arranged in a mode that the lower end of the plastic bottle is located at the height of 180cm above the ground, then the tail end of one side of the hose is connected with the lower end of the plastic bottle, the other side of the hose is guaranteed to be located at the operable height on the pet fixing bed, the tail end of the hose is inserted into the stomach of a pet in the operation process, and the phenomena of knotting, compression, backflow, high-low inversion and the like of the hose are guaranteed in the whole process of direct feeding. In the test, the speed-adjusting throttle valve of the hose was adjusted to a position where distilled water flowed at a flow rate of 200 g/min, and then the distilled water flowed into each product, and the passability was observed.
The results are shown in fig. 3, and the results show that the oral liquid of example 1 is substantially free of clogging by aggregates and has very good hose passage. The oral liquid without transfer factor and astragalus polysaccharide has less blocking and good hose passing performance. The trafficability of other compositions is inferior to that of the three, and the analysis is mainly because the oral liquid is in direct contact with gastric juice of the pet, and the pH change causes semi-solidification in an acid area in the stomach, so that the fluidity of the subsequent oral liquid is poor, and the application range of the product in specific practice is affected.
Example 4 therapeutic Effect detection of oral liquid for cat immune factor
Test pets: 40 pet cats infected with feline rhino-virus were tested by PCR and these samples were collected from the pet hospitals in 2016-2020 (divided into 5 groups containing water for injection as a negative control).
Dosing regimen:
experimental group: the medicaments are taken along with the food according to the dosage of 40 mg/kg for treatment by using famciclovir. The medicine is administered daily, and is administered daily for 10 days. 20ml of oral liquid is fed at the same time of treatment, twice daily until the treatment course is over (group 1).
Negative control: the same as the experimental group, but fed with water for injection (group 2).
Control group 1-3: the same experimental group, but with 20ml of control 1-3 product, fed (groups 3-5).
Curative effect judgment criteria: referring to literature efficacy criteria, (1) cure: symptoms and signs all disappeared; (2) obvious effect: all symptoms disappear or the main symptoms and signs disappear; (3) effective: the main symptoms and signs are basically disappeared; (4) ineffective: there was no improvement in symptoms or signs. The total score was calculated by scoring 8, 6, 4, and 2 according to the above criteria, respectively, and summarized as shown in Table 2.
Table 2 scoring condition and condition record for experimental group
| Group of | Healing | Has obvious effect | Effective and effective | Invalidation of | Total score |
| 1 | 7 | 1 | - | - | 62 |
| 2 | - | 1 | 3 | 4 | 26 |
| 3 | 1 | 3 | 3 | 1 | 40 |
| 4 | 1 | 3 | 2 | 2 | 42 |
| 5 | 2 | 2 | 4 | - | 44 |
From clinical experience, the treatment scheme of famciclovir is safer and more reliable under the condition of no other virus or bacterial infection, and obvious effects can be seen after 14 days of treatment, so that whether the oral liquid has a promoting effect on the use of medicines or not is observed by adopting a treatment scheme of less than 14 days in the test. The results show that after three treatment courses, the experimental group and the control group are obviously better than the negative control group, and the oral liquid provided by the application can effectively promote the drug treatment on cats, has the effect of improving the immunity of the cats, and is remarkable in curative effect and high in cure rate, wherein the effect of the experimental group is the best, 7 cases (87.5%) are cured, 1 case (12.5%) are effective, 0 case (0%) are ineffective, and the total effective rate is 100%. After 5 days of treatment, the peripheral limbal infiltrate began to decrease in density. There was no sign of breakthrough epithelial keratitis. After 7 days, the infiltrate continued to decrease and conjunctivitis had resolved. The infection was completely cured within 8 days as evidenced by normal ocular examination and color, and the pet cat resumed normal behavior and activity (see fig. 4).
While the foregoing embodiments have been described in some detail by way of illustration, it will be appreciated by those skilled in the art that changes, modifications, substitutions, combinations, simplifications, etc. may be made without departing from the principles of the present application, and such modifications may be considered equivalent and the scope of the application.
Claims (3)
1. A cat immune factor oral liquid is characterized in that the cat immune factor oral liquid contains transfer factors with the final concentration of 1-10mg/ml, astragalus polysaccharide 1-5%, sweetener 1-10%, sodium chloride 0.5-5%, taurine 0.1-1.0% and water for injection; wherein the sweetener is sucrose; the pH value of the cat immune factor oral liquid is 6.4-7.4, and the viscosity is below 50 cP; the particle size distribution of the cat immune factor oral liquid is in bimodal distribution, and at least 1 peak exists below the particle size of 500 nm; wherein the frequency of the 1 st peak with smaller particle size is higher than the frequency of the 2 nd peak with larger particle size in the bimodal distribution diagram,
the preparation method of the cat immune factor oral liquid comprises the following steps:
preparation of transfer factor I
(1) Cutting and picking: removing thawed canine spleen, bagging, strictly selecting according to appearance requirements in raw material standards, clamping fat by forceps, and shearing by scissors;
(2) Cleaning: accurately weighing the feeding amount of the sheared raw materials, cleaning the weighed raw materials with 0.8% NaCl solution for 2-3 times, and draining;
(3) Primary twisting: placing the raw materials into a charging hopper of a meat grinder, operating according to the operation rules of the meat grinder, primarily grinding for 1 time, and filling with a clean material barrel;
(4) Finish twisting: mixing the raw materials after primary twisting with water for injection according to the proportion of 1:1.5, placing the mixture into a charging hopper, grinding the mixture for 4 times according to the operation procedure of a colloid mill, preparing homogenate, placing the homogenate into a saline bottle or a plastic bottle with the pH of 4.8 regulated by 2mol/L HCl, repeatedly freezing and thawing for 6 times at the temperature of minus 20 ℃, and quickly thawing or naturally thawing the water for continuous use, wherein the temperature is lower than 37 ℃;
(5) And (3) centrifugal separation: centrifuging the freeze-thawed homogenate with a refrigerated centrifuge at 8000rpm at 4deg.C for 30min, discarding the precipitate, collecting supernatant, adjusting pH to 6.8 with 2mol/L NaOH, pre-filtering or freeze-preserving at-20deg.C;
(6) Prefiltering: ultrafiltering the supernatant with a prefilter with a molecular weight cut-off of 300KD after coarse filtration of 1um to obtain clear filtrate;
(7) Ultrafiltration: ultrafiltering the filtrate with ultrafiltration membrane with molecular weight cutoff of 10KD-0.5KD, collecting active polypeptide refined solution, quantifying, and storing;
precisely weighing astragalus polyose powder according to the weight proportion, adding a proper amount of water for injection, stirring until the astragalus polyose powder is completely dissolved, and performing primary filtration by using a 0.45um microporous filter;
III, transferring the astragalus polysaccharide solution into a liquid preparation tank, sequentially adding sucrose, potassium sorbate, sodium chloride, taurine and transfer factors prepared in the steps with corresponding weight, and stirring until the astragalus polysaccharide solution is completely dissolved;
IV, adding water for injection to a corresponding volume, stirring for 10-20 minutes, and adjusting the pH value to 6.4-7.4 by using hydrochloric acid or sodium hydroxide;
v using the solution obtained by ultrasonic treatment;
VI, sterilizing and filtering the liquid medicine by using a 0.22um microporous filter, and sub-packaging and storing;
wherein the step of using the solution obtained by ultrasonic treatment is specifically: cooling the solution to 0-4deg.C at a speed of 2-5deg.C/h, treating with 2KW and 1KHz for 15s, and repeating for 3-5 times at a gap of 10 s; treating with 3KW and 2KHz for 15s, and repeating for 3-5 times at a gap of 10 s; treating with 4KW and 2KHz for 10s, and repeating for 3-5 times at 10 s; finally, the mixture is treated for 15s with 4KW and 3KHz, the gap is 10s, the mixture is repeated for 3 to 5 times, and after incubation for 1h at 0 to 4 ℃, the mixture is returned to the room temperature at a speed of 2 to 5 ℃/h.
2. The oral liquid for cat immune factor according to claim 1, further comprising a preservative, wherein the preservative is potassium sorbate, and the weight percentage of the oral liquid in the pharmaceutical composition is 0.1-1%.
3. The use of the oral liquid of feline immune factor as defined in claim 1 in the preparation of a medicament for cats.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101167772A (en) * | 2006-10-26 | 2008-04-30 | 天津市润拓生物技术有限公司 | Health-care product with strengthening physique immunity for dog and cat |
| CN105030827A (en) * | 2015-07-14 | 2015-11-11 | 天津瑞普生物技术股份有限公司 | Transfer factor and application thereof |
| CN105687302A (en) * | 2014-11-28 | 2016-06-22 | 洛阳惠中兽药有限公司 | Traditional Chinese medicinal composition for dogs and cats and application of traditional Chinese medicinal composition |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101167772A (en) * | 2006-10-26 | 2008-04-30 | 天津市润拓生物技术有限公司 | Health-care product with strengthening physique immunity for dog and cat |
| CN105687302A (en) * | 2014-11-28 | 2016-06-22 | 洛阳惠中兽药有限公司 | Traditional Chinese medicinal composition for dogs and cats and application of traditional Chinese medicinal composition |
| CN105030827A (en) * | 2015-07-14 | 2015-11-11 | 天津瑞普生物技术股份有限公司 | Transfer factor and application thereof |
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| 关于我国畜牧业生产中限制抗生素的使用问题;万遂如;《兽医导刊》;20170315(第05期);"2 在动物预防保健中的应用" * |
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