Pet emotion inhibitor as well as preparation method and application thereof

Abstract

The invention discloses a pet emotion inhibitor and a preparation method and application thereof, and relates to the field of pet medicines.The long-acting pet emotion inhibitor comprises a silicone tube sleeve and a medicine core capable of being arranged in the silicone tube sleeve, and the medicine core comprises the following components: norethindrone, medicine core rubber compound and silicon dioxide; the product can simultaneously inhibit hormone and estrogen levels of pets, inhibit oestrus of pets, prevent pyoaccumulation of uterus and realize contraception, and provides a novel reversible contraception product and method for pets.

Description

Technical Field

[0001] The present invention belongs to the technical field of pet medicine, and in particular relates to a pet mood suppressant and a preparation method and application thereof. Background Art

[0002] The main methods of contraception for pets include surgical operation, chemical castration, immunocastration and hormone replacement. Among them, surgical castration is a conventional method for reproductive regulation of these animals. However, surgical operation has risks, and surgical sterilization is irreversible. In addition, existing hormone drugs generally reduce estrogen and increase progesterone to inhibit animals from entering estrus, but long-term use of drugs can also lead to infertility.

[0003] Pets in estrus, such as cats, tend to enter estrus frequently, and their endometrium thickens. In addition, the cervix of cats in estrus relaxes, making it easy for bacteria to invade. The thickened endometrium is a hotbed for bacterial growth, which makes cats susceptible to pyometra. Therefore, if estrus is not suppressed or controlled in time, it will lead to pyometra in pets. Summary of the invention

[0004] In view of the above situation, in order to overcome the defects of the prior art, the present invention provides a pet mood inhibitor, which can simultaneously suppress the progesterone and estrogen levels of pets, inhibit pet estrus, prevent uterine pyometra and contraception, and provide a new reversible contraceptive product and method for pets.

[0005] First, it was verified that the target drug in the plasma after administration had specificity and could be sustained-released in the plasma by embedding administration. A chromatographic peak with a good peak shape appeared in the cat plasma after administration, verifying that this method had good specificity.

[0006] Then, the effective dose of the preparation is confirmed and it is verified that the preparation can simultaneously inhibit the levels of progesterone and estrogen, inhibit the animals from entering the estrus period, and thus achieve the purpose of preventing pyometra, while achieving the contraceptive effect by inhibiting the estrogen level, and there is no conflict between the two.

[0007] Specifically, the present invention is realized by the following scheme: In the first aspect, the present invention provides a long-acting pet mood suppressant, comprising a silicone tube sleeve and a drug core that can be placed in the silicone tube sleeve, and the drug core comprises the following components: methyl norethindrone, drug core compound rubber and silicon dioxide.

[0008] Preferably, the drug core comprises the following components in parts by weight: 50-100 parts of norethindrone, 100-110 parts of drug core rubber mix and 15-20 parts of silicon dioxide.

[0009] Preferably, the drug core comprises the following components in parts by weight: 75 parts of norethindrone, 100-110 parts of drug core rubber mix and 15-20 parts of silicon dioxide.

[0010] In a second aspect, the present invention provides a method for preparing the long-acting pet mood suppressant proposed in the first aspect, comprising:

[0011] Step 1: The methyl norethindrone is refined before processing, mixed evenly according to the prescription of the core compound rubber, and then placed on a flat vulcanizer for vulcanization at 125-155°C and a pressure of 9-13Mpa for 60-70 minutes.

[0012] Step 2: Extrude the medical silicone rubber in the extruder cavity through a mold and process it into shape, and vulcanize it in a drying oven at 320-380°C. After the treatment, a silicone tube sleeve is obtained.

[0013] Step 3: Assembly of the core tube: It is completed through four processes: core trimming, swelling and tube loading, two-ton sealing, and adhesive cutting.

[0014] Step 4: Use independent packaging materials for packaging and sterilize with ethylene oxide after packaging.

[0015] In the third aspect, the present invention provides the use of the long-acting pet mood inhibitor proposed in the first aspect in the preparation of an animal estrus inhibitory drug. According to experimental results, the pet mood inhibitor proposed in the first aspect can reduce the progesterone level in the pet's body and control the occurrence of estrus. When the inhibitor is used at an effective concentration in clinical use, cats do not show estrus symptoms, and the purpose of preventing uterine pyometra is achieved at the same time.

[0016] In a fourth aspect, the present invention provides the use of the long-acting pet mood suppressant proposed in the first aspect in the preparation of animal contraceptive drugs. According to experimental results, an effective amount of the suppressant has been shown to reduce estrogen levels in pets, and when estrogen levels are reduced, ovulation is inhibited, thereby achieving the purpose of contraception.

[0017] In a fifth aspect, the present invention provides the long-acting pet mood suppressant proposed in the first aspect for use in simultaneously suppressing the levels of estradiol and progesterone in animal plasma.

[0018] In a sixth aspect, the present invention provides use of the long-acting pet mood suppressant proposed in the first aspect in the preparation of a drug for preventing feline pyometra.

[0019] In a seventh aspect, the present invention provides use of the long-acting pet mood suppressant proposed in the first aspect in the preparation of a contraceptive drug for cats.

[0020] In an eighth aspect, the present invention provides the long-acting pet mood suppressant proposed in the first aspect for use in simultaneously suppressing the levels of estradiol and progesterone in cat plasma.

[0021] Compared with the prior art, the present invention has the following beneficial effects: effectively reducing the level of progesterone, controlling the bacterial growth environment in the pet's uterus, thereby controlling the occurrence of estrus and achieving the effect of preventing uterine pyometra; achieving the effect of contraception by inhibiting the production of estrogen (inhibiting estrogen levels and inhibiting ovulation); being able to restore fertility, having a certain plasticity, and being able to quickly restore fertility after removing the silicone tube, providing a new reversible contraceptive product and method for pets, filling the gap in domestic pet non-surgical contraception, and having great theoretical and practical significance. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The accompanying drawings are used to provide further understanding of the present invention and constitute a part of the specification. They are used to explain the present invention together with the embodiments of the present invention and do not constitute a limitation of the present invention.

[0023] Figure 1 The chromatogram of the norgestrel standard solution in Example 5 (0.1 ng / mL) is shown in FIG.

[0024] Figure 2 is the blank plasma chromatogram in Example 5;

[0025] Figure 3 Chromatogram of blank plasma spiked with levonorgestrel (0.1 ng / mL) in Example 5;

[0026] Figure 4 This is a chromatogram of norethindrone in plasma of the experimental cat implanted with norethindrone silicone rod in Example 5;

[0027] Figure 5 This is a drug-time curve of norgestrel in experimental cat plasma in Example 6;

[0028] Figure 6 The weight changes of cats in each experimental group in Example 6;

[0029] Figure 7 This is a curve diagram of estrogen changes in cat plasma in Example 6;

[0030] Figure 8 This is a curve chart of progesterone changes in cat plasma in Example 6. DETAILED DESCRIPTION

[0031] The present invention discloses a pet mood suppressant and a preparation method and application thereof. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve the desired effect. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0032] Example 1

[0033] A long-acting pet mood suppressant, the drug core comprises the following components: 37.5 mg of norgestrel, 100-110 mg of drug core mixed rubber and 15-20 mg of silicon dioxide; silicone tube sheath material: about 60-80 mg of LS-4500 silicone rubber.

[0034] Adding an appropriate amount of silicon dioxide component into the drug core can improve the toughness of the drug core silicone rod and reduce the probability of breakage; the wall thickness of the silicone tube sleeve is 0.33-0.37mm.

[0035] Example 2

[0036] A long-acting pet mood suppressant, the drug core comprises the following components: 75 mg of norgestrel, 100-110 mg of drug core mixed rubber and 15-20 mg of silicon dioxide; the silicone tube sleeve material: about 60-80 mg of LS-4500 silicone rubber.

[0037] Example 3

[0038] A long-acting pet mood suppressant, the drug core comprises the following components: 150 mg of norgestrel, 100-110 mg of drug core mixed rubber and 15-20 mg of silicon dioxide; silicone tube sheath material: about 60-80 mg of LS-4500 silicone rubber.

[0039] Comparative Example 1

[0040] The inhibitor core includes the following components: 18.75 mg of norgestrel, 100-110 mg of core compound rubber and 15-20 mg of silicon dioxide; the silicone tube sheath material: about 60-80 mg of LS-4500 silicone rubber.

[0041] Comparative Example 2

[0042] The inhibitor core comprises the following components: 0 mg of norgestrel, 100-110 mg of core compound rubber and 15-20 mg of silicon dioxide; the silicone tube sheath material: about 60-80 mg of LS-4500 silicone rubber.

[0043] Embodiment 4:

[0044] The preparation method of the inhibitor prepared according to the composition ratio of each group of Examples 1-3 and Comparative Examples 1-2 is as follows:

[0045] Step 1: The methyl norethindrone is refined before processing, mixed evenly according to the prescription of the core compound rubber, and then placed on a flat vulcanizer for vulcanization at 125-155°C and a pressure of 9-13Mpa for 60-70 minutes.

[0046] Step 2: Extrude the medical silicone rubber in the extruder cavity through a mold and process it into shape, and vulcanize it in a drying oven at 320-380°C. After the treatment, a silicone tube sleeve is obtained.

[0047] Step 3: Assembly of the core tube: It is completed through four processes: core trimming, swelling and tube loading, two-ton sealing, and adhesive cutting.

[0048] Step 4: Use independent packaging materials for packaging and sterilize with ethylene oxide after packaging.

[0049] The drug cores of the pet inhibitor prepared according to the component ratios in Examples 1-3 and Comparative Examples 1-2 are respectively recorded as No. 1 silicone rod, No. 2 silicone rod, No. 3 silicone rod, No. 4 silicone rod and No. 5 silicone rod (placed in the prepared silicone tube sleeve when buried), refer to Table 1.

[0050] Table 1: Norethindrone content corresponding to the silica gel rods prepared in the examples and comparative examples

[0051]

[0052] Example 5: Methodological confirmation (specificity, detection line and quantitation limit determination, standard curve determination, recovery and precision determination).

[0053] (1) Specificity: Methyltestosterone was selected as the internal standard to prepare the internal standard working solution. Blank plasma, blank plasma with internal standard and norgestrel reference substance, and plasma samples after administration were selected. The three groups of samples were subjected to plasma pretreatment (for specific steps, refer to the detailed description later in this example), and the chromatograms were compared. The results were referenced to Figure 1-Figure 4 ; (The blank plasma and blank plasma with norgestrel and methyltestosterone standard samples added were extracted and prepared according to the sample pretreatment method and then measured).

[0054] in, Figure 1 The chromatograms of norgestrel and internal standard methyltestosterone in the standard solution show that the peaks of the two compounds are good, and the retention times are 3.33min and 3.06min, respectively.

[0055] Figure 2 is the blank plasma chromatogram;

[0056] Figure 3 Chromatogram of the standard substance of methylnorethindrone and internal standard methyltestosterone added to blank plasma; the concentration of methylnorethindrone added was 0.1ng / ml, and the concentration of methyltestosterone added was 2ng / ml. Figure 2 and Figure 3 By comparison, no chromatographic peaks appeared at the retention times of norethindrone and methyltestosterone in the blank plasma chromatogram, proving that there was no interference from other peaks at the target drug.

[0057] exist Figure 4 The plasma chromatogram after implanting a norgestrel silicone rod (No. 2 silicone rod, norgestrel content of 75 mg) in a cat showed that the plasma sample after administration showed chromatographic peaks with good peak shapes, which were judged to be norgestrel and methyltestosterone based on the retention time, further proving that this method has good specificity.

[0058] In this example, the preparation of the standard working solution of norgestrel is as follows: (1) Norgestrel standard stock solution (1 mg / mL): Accurately weigh 10.0 mg of norgestrel reference substance, dissolve it in acetonitrile and dilute to the mark in a 10 mL volumetric flask to prepare a standard stock solution with a concentration of 1 mg / mL. Store at 4°C and the shelf life is 3 months. (2) Preparation of working solution: Take 0.5 mL of norgestrel standard stock solution in a 50 mL volumetric flask and dilute to the mark in acetonitrile. Store at 4°C and the shelf life is 1 month.

[0059] Preparation of methyltestosterone standard working solution: (1) Methyltestosterone standard stock solution (1 mg / mL): Accurately weigh 10.0 mg of methyltestosterone reference substance, dissolve it in acetonitrile and dilute to the mark in a 10 mL volumetric flask to prepare a standard stock solution with a concentration of 1 mg / mL. Store at 4°C, with a shelf life of 3 months; (2) Methyltestosterone working solution (10 μg / mL): Take 0.5 mL of methyltestosterone stock solution in a 50 mL volumetric flask and dilute to the mark in acetonitrile. Store at 4°C, with a shelf life of 1 month.

[0060] The pretreatment method of experimental cat plasma samples was as follows: 100 μL of plasma was taken, 10 μL of internal standard working solution was added, and mixed. 500 μL of extracting solution was added, and the extracting solution was acetonitrile, which was an organic solvent. After shaking, vortexing was performed for 10 minutes, ultrasonication was performed for 10 minutes, and the supernatant was taken to another clean centrifuge tube after centrifugation, and dried with nitrogen. The residue was re-dissolved with 200 μL of the initial proportion mobile phase, and filtered through a 0.22 μm filter membrane after thorough vortexing, and then tested on the machine.

[0061] Instruments and equipment: liquid chromatography-tandem mass spectrometer (ACQUITY LC-MS / MS, WATERS, USA), CNC ultrasonic cleaner (KQ-500DE, Kunshan Ultrasonic Instrument Co., Ltd.), high-speed centrifuge (CT15RE, Hitachi Koki Co, Ltd), nitrogen evaporator (N-Evap nitrogen evaporator, Berlin), electronic balance (AE240, Mettler-Toledo), etc.

[0062] Chromatographic conditions:

[0063] Chromatographic column, ACQUITY UPLCBEH C18, 2.1×100 mm, 5 μm; mobile phase, phase A is 0.1% formic acid in water; phase B is 0.1% formic acid in acetonitrile; flow rate, 0.2 mL / min; column temperature, 30°C; injection volume, 10 μL; gradient elution, the gradient elution program is shown in Table 2.

[0064] Table 2: Gradient elution conditions

[0065] Time (min) Flow rate (mL / min) Mobile phase A (%) Mobile phase B (%) 0 0.2 50 50 3 0.2 5 95 5 0.2 5 95 5.1 0.2 50 50 8 0.2 50 50

[0066] Mass spectrometry conditions:

[0067] Ion source, electrospray ion source; scanning mode, positive ion scanning; detection mode, multiple reaction monitoring; ionization voltage, 3.0 kV; nebulization temperature, 350 °C; nebulization gas flow rate, 540 L / h; the qualitative and quantitative ion pairs of the tested drugs and the corresponding fragmentation voltages and collision energies are shown in Table 3.

[0068] Table 3: Qualitative and quantitative ions, fragmentation voltages, and collision energies of norgestrel and methyltestosterone

[0069]

[0070] (2) Detection line and quantitation limit determination

[0071] A certain amount of norgestrel and internal standard methyltestosterone reference substance were simultaneously added to blank cat plasma to prepare a series of samples. After the sample was pretreated according to the method mentioned in part (1) of this example, the liquid chromatography-tandem mass spectrometry (LC-MS / MS) method was used for detection under the instrument conditions shown in part (1) of this embodiment. The minimum concentration with a signal-to-noise ratio S / N of not less than 3 was used as the detection limit (LOD), and the minimum concentration with a signal-to-noise ratio S / N of not less than 10 was used as the quantification limit (LOQ).

[0072] In this detection method, the quantification limit of norgestrel in plasma is 0.1 ng / mL; the detection limit is 0.05 ng / mL.

[0073] (3) Standard curve determination

[0074] In the blank cat plasma matrix, add internal standard methyltestosterone and different amounts of methylnorgestrel working solution to draw a standard curve of methylnorgestrel. The plasma matrix is ​​prepared with methylnorgestrel concentrations of 0.05, 0.125, 0.25, 0.5, 2.5, and 5 ng / mL, and the internal standard methyltestosterone concentration is 1 ng / mL for LC-MS / MS determination. With the measured quantitative ion mass chromatographic peak area of ​​methylnorgestrel as the ordinate and the corresponding methylnorgestrel concentration as the abscissa, draw a standard curve and calculate the regression equation and correlation coefficient.

[0075] The regression equation of the standard curve in plasma is y=0.298614*x+0.037282, and the correlation coefficient is r 2 >0.99. This indicates that the plasma concentration of levonorgestrel has good linearity in the range of 0.1-10 ng / mL.

[0076] (4) Recovery and precision determination

[0077] Blank spiked samples were prepared by adding different amounts of norgestrel working solution to 100 μL blank cat plasma, corresponding to plasma concentrations of 0.2, 1, and 5 ng / mL, respectively. Three batches were prepared for each concentration, with 5 parallels for each batch. These samples were used to detect the retention time of the target drug and evaluate the recovery rate and coefficient of variation.

[0078] Take the blank spiked plasma sample prepared in 3.2.7, process and determine it according to the above method, and calculate the recovery rate and coefficient of variation of norgestrel in the plasma sample. The recovery rate and coefficient of variation of plasma samples are shown in Table 4. From the results in Table 4, it can be seen that the RSD values ​​of the intra-batch precision and inter-batch precision of this method are less than 15%, and the precision meets the requirements. The recovery rates of the three concentrations of high, medium and low, 5, 1, and 0.2 ng / mL are all between 80% and 120%, which meets the requirements.

[0079] Table 4: Recovery and precision of norgestrel extraction in plasma

[0080]

[0081] Example 6: Animal experiments were conducted on Examples 1-3 and Comparative Examples 1-2 to verify the blood concentration of norgestrel in animals; and to verify the effective dosage and application of long-acting pet inhibitors.

[0082] Based on the above purposes, animal experiments mainly include four aspects: one is to detect the blood concentration of norgestrel at different time points before and after medication in experimental animals; the second is the effect of norgestrel on the body weight of experimental animals before and after medication; the third is to detect the concentration of estradiol and progesterone in the plasma of experimental animals at different time points before and after medication; the fourth is to clinically observe the estrus symptoms of animals.

[0083] Experimental animal selection: Experimental cats were purchased from Jixiang Cattery in Benxi City, Liaoning Province. The breeds were British shorthair series including blue cat, blue and white, silver gradient, calico and ragdoll, etc. The cats were 7 months to 1.5 years old, including 10 male cats and 50 female cats;

[0084] Experimental grouping: (select all female cats, n=10 per group)

[0085] Group 1, No. 3 silicone rod was implanted subcutaneously; n = 10;

[0086] Group 2, No. 2 silicone rod was implanted subcutaneously; n = 10;

[0087] Group 3, No. 1 silicone rod was implanted subcutaneously; n = 10;

[0088] Group 4, No. 4 silicone rod was implanted subcutaneously; n = 10

[0089] The fifth group (blank control group) had No. 5 silicone rod implanted subcutaneously; n=10.

[0090] (1) Detection of the first aspect: For the first to fourth groups of cats, each cat was weighed and a blank blood sample was collected before administration. After administration, about 1.5 mL of blood was collected from the forearm vein at 4 h, 1, 3, 7, 14, 21, 28, 35, 42, 56, and 70 d, respectively, and placed in an anticoagulant tube. The plasma was separated by centrifugation at 3000 r / min × 10 min and stored in a -20°C refrigerator until the blood concentration of norgestrel at different time points in the experimental cats was measured.

[0091] Test result reference Figure 5 As shown in Table 5, since the dosage of each cat in the same experimental group was the same, but there were differences in weight and breed among the cats, the peak concentration and peak time of norgestrel in the plasma of the experimental cats were different. Figure 5 It can be seen that:

[0092] In the first group of experimental cats, the blood drug concentration reached a stable state on the 42nd day after the No. 3 silicone rod (containing 150 mg of norgestrel) was implanted;

[0093] In the experimental cats of group 2, the blood drug concentration reached a stable state on the 35th day after implantation of No. 2 silicone rod (norethindrone content 75 mg);

[0094] The blood drug concentration of the experimental cats in Group 3 and Group 4 reached a stable state on the 28th day after implantation of No. 1 silicone rod (methyl norethindrone content of 37.5 mg) and No. 4 silicone rod (methyl norethindrone content of 18.75 mg), respectively.

[0095] Table 5: Maximum plasma concentrations of norgestrel in cats from Group 1 to Group 4

[0096]

[0097] (2) The second aspect of the test was the effect of norgestrel on the body weight of experimental animals before and after the test.

[0098] The weight of each cat was weighed before and after the experiment. Figure 6 .Depend on Figure 6 It can be seen that when the experimental cats were implanted with silicone rods No. 1, No. 2, and No. 3 (Groups 1 to 3), the weight of the experimental cats increased. The average weight of the experimental cats in Group 4 implanted with silicone rod No. 4 and Group 5 implanted with silicone rod No. 5 decreased significantly.

[0099] When the experimental cats were implanted with silicone rods No. 1, 2, and 3 (the first to third groups), they were mentally quiet and showed no signs of estrus. However, the experimental cats implanted with silicone rod No. 4 and silicone rod No. 5 (blank silicone rod) showed signs of estrus. During estrus, they were irritable, walked around in the cage, rubbed their bodies against the cage, and had poor appetite during estrus, which led to weight loss.

[0100] (3) Detection of the third aspect: Blood samples of the cats in the first to fifth groups were collected at 14, 28, 42, 56, and 70 days after administration and were used to detect the concentrations of estradiol and progesterone in plasma. Blood samples of the experimental cats in each group were collected before and after administration at different time points, 14, 28, 42, 56, and 70 days, and the concentrations of estradiol and progesterone in plasma were detected by radioactive labeling.

[0101] (4) Clinical trial: observe whether five groups of female cats are in estrus, and randomly select female cats in estrus to mate with male cats. During the trial, try to put the female cats in estrus and male cats in the same cat cage for observation. The observation results are shown in Table 6.

[0102] Changes of estradiol and progesterone concentrations in cat plasma over time Figure 7 , Figure 8 As shown, according to the experimental results, after the No. 3 silicone rod, No. 2 silicone rod, and No. 1 silicone rod were subcutaneously implanted in the first, second, and third groups of experimental cats, respectively, the concentrations of estradiol and progesterone in the cats' plasma remained stable after 42 days, and no estrus symptoms were shown clinically;

[0103] In the fourth group (with No. 4 silicone rod implanted subcutaneously), the concentrations of estradiol and progesterone in the cats' plasma fluctuated greatly. Clinically, 80% of the cats showed estrus symptoms, rubbing their bodies against the cages, stimulating their genitals, and showing obvious stepping behavior of their hind legs, showing irritability.

[0104] Compared with the drug-treated group, the plasma estradiol and progesterone levels of cats in the blank control group remained at a high level, and 100% of the cats showed estrus symptoms.

[0105] The female cats in estrus were randomly selected to mate with male cats, and they successfully conceived and gave birth to kittens. During the experiment, female cats that were not in estrus were placed in the same cat cage with male cats. It was found that when the male cat in estrus approached the female cat, the female cat became furious and waved her front legs to hit the male cat, refusing the male cat to approach. In this case, it was difficult to complete mating.

[0106] In this embodiment, the detection of estrogen and progesterone in cat plasma was commissioned to Shanghai Xinfan Biotechnology Co., Ltd. The instrument used was the XH6080 radioimmunoassay instrument of Xi'an Nuclear Instrument Factory. The radioimmunoassay method referred to the instructions of the kit. The standard and sample (100 μL) were added with the marker antibody and incubated at 37°C for 2 hours. After adding the separation agent for 15 minutes, the mixture was centrifuged at 3800 rpm for 15 minutes, and the supernatant was taken for detection.

[0107] Table 6: Clinical observations and test results

[0108]

[0109] The above experimental results verify that the silicone rod prepared according to the composition ratio of Examples 1-3 is implanted subcutaneously, and the sustained release of norgestrel in cats is stable. During the sustained release period, the levels of estradiol and progesterone in cats are suppressed, the estrus of cats is suppressed, and diseases such as pyometra of cats can be prevented. The mood suppressant has a long-lasting effect, a stable dissolution rate, and a sustained release period of more than three years in the body. During the sustained release period, the estrogen level is suppressed and ovulation is suppressed to achieve the purpose of contraception. After the silicone rod is removed, conception can be restored, replacing surgical contraception and other means, providing pets with new reversible contraceptive products and methods, filling the gap in non-surgical contraception for domestic pets, and having great theoretical and practical significance.

[0110] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A long-acting pet mood suppressant, characterized in that: The invention comprises a silicone tube sleeve and a medicine core which can be placed in the silicone tube sleeve. The medicine core comprises the following components: methyl norethindrone, medicine core mixed rubber and silicon dioxide.

2. A long-acting pet mood suppressant according to claim 1, characterized in that: The drug core comprises the following components in parts by weight: 37.5-150 parts of norethindrone, 100-110 parts of drug core mixed rubber and 15-20 parts of silicon dioxide.

3. A long-acting pet mood suppressant according to claim 1, characterized in that: The drug core comprises the following components in parts by weight: 75 parts of norethindrone, 100-110 parts of drug core mixed rubber and 15-20 parts of silicon dioxide.

4. A method for preparing a long-acting pet mood suppressant according to any one of claims 1 to 3, characterized in that: include: Step 1: The methyl norethindrone is refined before processing, mixed evenly according to the prescription of the core compound rubber, and then placed on a flat vulcanizer for vulcanization at 125-155°C and a pressure of 9-13Mpa for 60-70 minutes; Step 2: Extruding the medical silicone rubber in the extruder cavity through a mold to form the material, and vulcanizing it at 320-380° C. in a drying oven; after the treatment, a silicone tube sleeve is obtained; Step 3: Assembly of the core tube: It is completed through four processes: core trimming, swelling and tube loading, two-ton sealing, and adhesive cutting; Step 4: Use independent packaging materials for packaging and sterilize with ethylene oxide after packaging.

5. Use of a long-acting pet mood suppressant according to any one of claims 1 to 3 in the preparation of a drug for suppressing animal estrus.

6. Use of a long-acting pet mood suppressant according to any one of claims 1 to 3 in the preparation of animal contraceptive drugs.

7. A long-acting pet mood suppressant according to any one of claims 1 to 3, used for simultaneously suppressing the levels of estradiol and progesterone in animal plasma.

8. Use of a long-acting pet mood suppressant according to any one of claims 1 to 3 in the preparation of a drug for inhibiting cat estrus.

9. Use of a long-acting pet mood suppressant according to any one of claims 1 to 3 in the preparation of a cat contraceptive drug.

10. A long-acting pet mood suppressant according to any one of claims 1 to 3, used for simultaneously suppressing the levels of estradiol and progesterone in cat plasma.

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