CN115282128A - Cat face pheromone gel ball and preparation method thereof - Google Patents

Cat face pheromone gel ball and preparation method thereof Download PDF

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CN115282128A
CN115282128A CN202210921953.6A CN202210921953A CN115282128A CN 115282128 A CN115282128 A CN 115282128A CN 202210921953 A CN202210921953 A CN 202210921953A CN 115282128 A CN115282128 A CN 115282128A
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pheromone
solution
gel
sodium alginate
ethanol
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CN115282128B (en
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张晓露
焦玉珠
唐海丽
王彦超
陈欣雨
高子朔
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Shanghai Frey Bio Technology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
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    • A61K31/23Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/231Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
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    • A61K9/5036Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract

The invention discloses a cat face pheromone gel ball and a preparation method thereof, wherein the cat face pheromone gel ball comprises the following steps: mixing pheromone and ethanol according to the volume ratio of 1 to 2.5, then adding the ethanol solution of the pheromone into a 4-6% sodium alginate solution, wherein the volume ratio of the ethanol solution of the pheromone to the sodium alginate solution is 1 to 2.5, and carrying out ultrasonic treatment on the obtained mixed solution to obtain a sodium alginate emulsion containing the pheromone; dripping the sodium alginate emulsion containing the pheromone into 2-3% of multivalent cation solution, and solidifying the gel to form gel ball particles to prepare the cat face pheromone gel balls. The pheromone is emulsified by an ultrasonic emulsification method without introducing any additive, and then is gelled to obtain the gel spheres with millimeter sizes. The pheromone gel ball provided by the invention is not limited in use scene, does not need to be plugged, and is suitable for long-distance and short-distance scenes; the gel ball can play a role in slow release, can release a plurality of components at the same time, has consistent release rate of the plurality of components, and can keep playing a role for a long time.

Description

Cat face pheromone gel ball and preparation method thereof
Technical Field
The invention relates to the technical field of biology, in particular to a cat face pheromone gel ball and a preparation method thereof.
Background
Pheromones (pheromones) are substances which are secreted by an individual to the outside of the body and which are detected by the olfactory organs of other individuals of the same species, causing the latter to exhibit a change in some behavioral, emotional, psychological or physiological mechanism. Pheromones are usually distributed in the body fluids of cats, including urine, sweat, specialized exocrine glands, and mucous membranes of the reproductive organs, all of which derive a field of odor labeling them, and this territorial marking facilitates communication between cats and the surrounding environment.
It is common in life for cats to rub their faces on objects, individuals, or on specific areas, in order to mark individuals or objects in their area. Cats have many sebaceous glands around their mouth, on the chin, in the ear canal, in the perianal area and on the tail, which leaves their chemical odor when rubbed against an object or individual. The presence of these odors allows the cat to become familiar with the surrounding environment and prevents anxiety in the cat.
The prior art has some semiochemicals for preventing stress, anxiety and aggressive behaviors between cats, the semiochemicals contain dimethyl pimelate and dimethyl azelate, have high unit price and high volume production cost, are not suitable for scenes with changed cat surrounding environment, and relieve or relieve the stress behaviors of cats in new environment, such as abnormal emotions and even pathological diseases. CN202011445267.3 discloses a cat face pheromone analogue comprising: methyl laurate, methyl myristate, methyl palmitate, methyl oleate, methyl linoleate, and dimethyl sebacate. The pheromone is suitable for scenes with changed cat surrounding environment, and can relieve or relieve the stress behavior of the cat in a new environment.
However, the applicant has found that the above prior art has at least the following technical problems: the pheromone in the prior art exists in a liquid form, and the pheromone is used in a spray form for a short time, so that the pheromone only can play a role in immediately relieving stress behaviors, but cannot play a role in long-term effectiveness. The electric heating device is generally adopted to promote the volatilization of the liquid pheromone for long-distance use, but the electric heating device is troublesome to use, needs to be charged or a battery, has more limitations, and is inconvenient to carry and transport in a liquid form.
Disclosure of Invention
The invention aims to provide a novel cat facial pheromone gel ball which is convenient to carry and transport, can play a slow-release role, can simultaneously and slowly release a plurality of components, has consistent release rate of the components and prolongs the action time.
The technical scheme adopted by the invention is as follows:
a method for preparing a cat facial pheromone gel sphere, comprising the following steps:
(1) Preparing a multivalent cation solution with the mass fraction of 4-6%, wherein the solvent is water; the cation in the multivalent cation solution is Ca 2+ 、Sr 2+ 、Ba 2+ 、Pb 2+ 、Cu 2+ 、Ni 2+ 、Zn 2+ 、Mn 2+ Wherein the anion is chloride;
(2) Preparing a sodium alginate solution with the mass fraction of 2-3%, wherein the solvent is water;
(3) Mixing pheromone and ethanol according to the volume ratio of 1 to 2.5, then adding the ethanol solution of the pheromone into the sodium alginate solution, wherein the volume ratio of the ethanol solution of the pheromone to the sodium alginate solution is 1 to 2.5, and carrying out ultrasonic treatment on the obtained mixed solution to obtain sodium alginate emulsion containing the pheromone;
(4) And (2) dropwise adding sodium alginate emulsion containing pheromone into the multivalent cation solution obtained in the step (1), solidifying the gel to form gel ball particles, filtering out the particles, cleaning and drying to obtain the cat face pheromone gel balls.
The pheromone comprises the following components: one or more of methyl laurate, methyl myristate, methyl palmitate, methyl oleate, methyl linoleate and dimethyl sebacate.
Preferably, the pheromone is one or a mixture of methyl linoleate, methyl myristate and methyl laurate.
In the step (1), the multivalent cation solution is preferably a calcium chloride solution.
In the step (1), the mass fraction of the multivalent cation solution is preferably 4.3 to 5.5%.
In the step (2), when preparing the sodium alginate solution, the sodium alginate solution is generally prepared by adding the sodium alginate into water according to the proportion, stirring and dissolving at 90 ℃, cooling, and standing overnight.
In the step (2), the mass fraction of the sodium alginate solution is preferably 2%.
In the step (3), the volume ratio of pheromone to ethanol is preferably 1.
The volume ratio of the ethanol solution of pheromone to the sodium alginate solution is preferably 1.
In the step (4), when dripping, syringes or droppers with different sizes can be adopted for dripping to obtain gel balls with the particle size diameter of 2-12 mm.
The preferred particle size of the gel beads is 2 to 4mm.
The sodium alginate emulsion containing the pheromone is preferably dropped using a 10mL syringe to obtain gel beads having a particle diameter of 2 to 4mm.
The invention also provides the cat face pheromone gel ball prepared by the preparation method.
The cat facial pheromone gel ball prepared by the invention is spherical or irregular oval, and the particle size of the gel ball particle is 2-12 mm, preferably 2-4 mm.
In the step (3), the obtained mixed solution is subjected to ultrasonic treatment for 2-3h under the power of 400W to prepare uniform pheromone-coated gel spheres. If the ultrasonic time is too short, the prepared gel spheres have uneven sizes, and air bubbles exist on the surfaces of the gel spheres, so that pheromone is unevenly distributed in the gel spheres, and the slow release effect is influenced.
The pheromone components of the invention are mostly esters with more than 10 carbon chains, and the water solubility is poor, so the pheromone is emulsified by an emulsion method through an ultrasonic emulsification method, no additive is introduced, and then the pheromone is gelled to obtain a gel ball with millimeter size, and the size of the ball influences the release speed of the pheromone, namely the release concentration in unit time. The slow release curves of the gel spheres with different sizes can show that the smaller the size of the gel spheres, the faster the slow release speed.
The pheromone gel ball provided by the application is not limited to a use scene, does not need to be plugged, and is suitable for long-distance and short-distance scenes; moreover, the gel balls can play a sustained-release role, can release a plurality of components at the same time, have consistent release rate of the plurality of components and can keep playing a role for a long time.
Drawings
FIG. 1 shows pheromone-coated gel beads prepared in example 1.
FIG. 2 is a graph showing the sustained release of the pheromone of example 1 at 15 ℃.
FIG. 3 shows pheromone-coated gel beads prepared in example 2.
FIG. 4 is a graph of the sustained release of the pheromone of example 2 at 38 ℃.
FIG. 5 is a graph of the sustained release of the pheromone of example 3 at 38 ℃.
FIG. 6 is a graph of the sustained release of the pheromone of example 4 at 38 ℃.
FIG. 7 is a graph of the sustained release of the pheromone of example 5 at 38 ℃.
FIG. 8 is a graph of the sustained release of the pheromone of example 6 at 38 ℃.
Fig. 9 shows pheromone-encapsulated heterogeneous gel beads prepared in comparative example 1.
Detailed Description
The technical solution of the present invention is described in detail below by specific examples, but the scope of the present invention is not limited thereto.
In the examples of the present invention, the pheromone one used was a mixture of 1 part by mass of methyl myristate and 1.86 parts by mass of methyl linoleate, and the pheromone two used was a mixture of 1 part by mass of methyl laurate and 1.86 parts by mass of methyl linoleate.
Example 1
(1) Adding 0.5549g of anhydrous CaCl 2 Dissolving in 10ml water to form uniform CaCl 2 A solution;
(2) Preparing a sodium alginate solution, wherein 0.2g of sodium alginate is added into 9.8ml of water, stirred and dissolved at the water bath temperature of 90 ℃, cooled and kept stand overnight;
(3) Adding 0.5ml of first pheromone (package label of mailing) into 1.0ml of ethanol, and mixing; then adding the pheromone ethanol solution into the sodium alginate solution (3.0 ml), and carrying out ultrasonic treatment for 2h at 400W to obtain a sodium alginate emulsion containing the pheromone;
(4) Extracting the above sodium alginate emulsion with 10ml needle tube, and dropwise adding into CaCl 2 Forming uniform pheromone-coated gel spheres in an aqueous solution, wherein the particle size of the gel spheres is about 2-4mm as shown in figure 1;
(5) The invention adopts a gas chromatography-mass spectrometer to detect a slow release curve chart of the pheromone at 15 ℃, and the experimental result is shown in figure 2.
In the sustained release graph, the ordinate represents the content of the remaining pheromone after the pheromone is released (initial concentration normalization is 100%), that is, the percentage of the content of the remaining pheromone after the release, and the smaller the final percentage, the more the pheromone is released.
Example 2
(1) Adding 0.45g of anhydrous CaCl 2 Dissolving in 10ml water to form uniform CaCl 2 A solution;
(2) Preparing a sodium alginate solution, wherein 0.2g of sodium alginate is added into 9.8ml of water, stirred and dissolved at the water bath temperature of 90 ℃, cooled and kept stand overnight;
(3) Adding 0.5ml of the first pheromone (package label of mailing) into 1.0ml of ethanol, and mixing; then adding the pheromone ethanol solution into the sodium alginate solution (3.0 ml), and carrying out ultrasonic treatment for 2h at 400W to obtain a sodium alginate emulsion containing the pheromone;
(4) Extracting the sodium alginate emulsion with a large-aperture dropper, and dropwise adding into CaCl 2 In aqueous solution, a uniform pheromone-coated gel bead was formed, as shown in FIG. 3. The particle size of the gel balls is about 8-12 mm;
(5) The invention adopts a gas chromatography-mass spectrometer to detect a sustained release curve chart of the pheromone which is sustained and released for 8 hours at 38 ℃, and the experimental result is shown in figure 4.
The results of figure 4 show that the slow release speed of the gel spheres is slow, and the content of the residual pheromone after 8 hours of slow release at 38 ℃ is about 40-50%.
Example 3
(1) Adding 0.55g of anhydrous CaCl 2 Dissolving in 10ml water to form uniform CaCl 2 A solution;
(2) Preparing a sodium alginate solution, wherein 0.2g of sodium alginate is added into 9.8ml of water, stirred and dissolved at the water bath temperature of 90 ℃, cooled and kept stand overnight;
(3) Adding 0.5ml of the first pheromone into 1.0ml of ethanol, and mixing and dissolving; then adding the pheromone ethanol solution into the sodium alginate solution (3.0 ml), and carrying out ultrasonic treatment at 400W for 2h to obtain a sodium alginate emulsion containing the pheromone;
(4) Extracting the above sodium alginate emulsion with 10ml needle tube, and dropwise adding into CaCl 2 In the water solution, gel balls which are uniform and wrap the pheromone are formed. The particle size of the gel balls is about 2-4 mm;
(5) The invention adopts a gas chromatography-mass spectrometer to detect a sustained release curve of the pheromone which is sustained and released for 2 hours at 38 ℃, and the experimental result is shown in figure 5.
Example 4
(1) Adding 0.45g of anhydrous CaCl 2 Dissolving in 10ml water to form uniform CaCl 2 A solution;
(2) Preparing a sodium alginate solution, wherein 0.2g of sodium alginate is added into 9.8ml of water, stirred and dissolved at the water bath temperature of 90 ℃, cooled and kept stand overnight;
(3) Adding 0.5ml of the first pheromone into 1.0ml of ethanol, and mixing and dissolving; then adding the pheromone ethanol solution into the sodium alginate solution (3.0 ml), and carrying out ultrasonic treatment for 2h to obtain sodium alginate emulsion containing the pheromone;
(4) The sodium alginate emulsion was extracted with a 10ml syringe and added dropwise to CaCl 2 In the water solution, gel balls which are uniform and wrap the pheromone are formed. The particle size of the gel balls is about 2-4 mm;
(5) The invention adopts a gas chromatography-mass spectrometer to detect a sustained release curve of the pheromone which is sustained and released for 8 hours at 38 ℃, and the experimental result is shown in figure 6.
Comparing example 2 with example 4, and comparing FIG. 4 with FIG. 6, the result shows that the slow release speed of the gel beads with 2-4mm is faster when other conditions are consistent, the residual pheromone content is about 20% after 8h of slow release at 38 ℃, and the release amount is higher than that of the gel beads with example 2. Therefore, the slow release effect of the gel pellets of 2-4mm is optimal.
Figure BDA0003777929980000071
Example 5
(1) Adding 0.45g of anhydrous CaCl 2 Dissolving in 10ml water to form uniform CaCl 2 A solution;
(2) Preparing a sodium alginate solution, wherein 0.2g of sodium alginate is added into 9.8ml of water, stirred and dissolved at the water bath temperature of 90 ℃, cooled and kept stand overnight;
(3) Adding 0.5ml of the first pheromone into 1.5ml of ethanol, and mixing and dissolving; then adding the pheromone ethanol solution into the sodium alginate solution (3.0 ml), and carrying out ultrasonic treatment for 2h to obtain a sodium alginate emulsion containing the pheromone;
(4) The sodium alginate emulsion was extracted with a 10ml syringe and added dropwise to CaCl 2 Forming uniform pheromone-wrapped gel balls in the aqueous solution, wherein the particle size of the gel balls is about 2-4 mm;
(5) The invention adopts a gas chromatography-mass spectrometer to detect a sustained release curve of the pheromone for 24 hours at 38 ℃, and the experimental result is shown in figure 7.
Example 6
(1) Adding 0.55g of anhydrous CaCl 2 Dissolving in 10ml water to form uniform CaCl 2 A solution;
(2) Preparing a sodium alginate solution, wherein 0.2g of sodium alginate is added into 9.8ml of water, stirred and dissolved at the water bath temperature of 90 ℃, cooled and kept stand overnight;
(3) Adding 0.5ml of second pheromone (package label of mailing) into 1.0ml of ethanol, and mixing; then adding the pheromone ethanol solution into the sodium alginate solution (3.0 ml), and carrying out ultrasonic treatment at 400W for 2h to obtain a sodium alginate emulsion containing the pheromone;
(4) The sodium alginate emulsion was extracted with a 10ml syringe and added dropwise to CaCl 2 Forming uniform pheromone-coated gel pellets in an aqueous solution, wherein the particle size of the gel pellets is about 2-4 mm;
(5) The invention adopts a gas chromatography-mass spectrometer to detect a sustained release curve of the pheromone which is sustained and released for 2 hours at 38 ℃, as shown in figure 8.
Comparative example 1
(1) Adding 0.45g of anhydrous CaCl 2 Dissolving in 10ml water to form uniform CaCl 2 A solution;
(2) Preparing a sodium alginate solution, wherein 0.2g of sodium alginate is added into 9.8ml of water, stirred and dissolved at the water bath temperature of 90 ℃, cooled and kept stand overnight;
(3) 0.5ml of the first pheromone is added into 1.0ml of ethanol and mixed. Then adding the pheromone ethanol solution into the sodium alginate solution (3.0 ml), and carrying out 400W ultrasonic treatment for 5min to obtain a sodium alginate emulsion containing the pheromone;
(4) Extracting the above sodium alginate emulsion with 10ml needle tube, and dropwise adding into CaCl 2 In the aqueous solution, the size of the gel beads encapsulating the pheromone was not uniform, as shown in FIG. 9.
The results in FIG. 9 show that the prepared gel beads have uneven sizes and air bubbles exist on the surfaces, which causes uneven distribution of pheromone in the gel beads and influences the slow release performance of the product.
Comparing example 1 with example 5, and FIGS. 2 and 7, it can be seen that the sustained release at 15 ℃ for 60h was 85%, and the sustained release at 38 ℃ for 24h was 93%, so that the higher the ambient temperature, the more advantageous the sustained release.
Comparing the example 1 with the example 7, and the graph 1 and the graph 9, the gel ball which is evenly wrapped with the pheromone can be prepared under the condition that the power and the time of the ultrasonic wave meet 400W and 2h-3 h, and the controllable slow release effect can be realized.
Comparative example 3 and example 5, FIGS. 5 and 7, caCl 2 The concentration of (a) has a certain influence on the slow release of the gel beads. 5.5% of CaCl 2 The slow release of the solution reaches 52 percent in 2 hours, and 4.5 percent of CaCl 2 The slow release of the solution is less than 20% at 2h, so the best CaCl 2 The mass fraction of the solution is 5.5%.
While the foregoing is directed to the preferred embodiment of the present application and is not intended to be limiting in any way, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined by the appended claims. Those skilled in the art should appreciate that they can readily use the disclosed conception and specific embodiments as a basis for designing or modifying other structures for carrying out the same purposes of the present invention without departing from the spirit and scope of the invention; meanwhile, any equivalent changes, modifications and evolutions of the above embodiments according to the essential technology of the present application are still within the scope of the technical solution of the present application.

Claims (10)

1. A preparation method of cat face pheromone gel balls is characterized by comprising the following steps:
(1) Preparing a multivalent cation solution with the mass fraction of 4-6%, wherein the solvent is water; the cation in the multivalent cation solution is Ca 2+ 、Sr 2+ 、Ba 2+ 、Pb 2+ 、Cu 2+ 、Ni 2+ 、Zn 2+ 、Mn 2+ Wherein the anion is chloride;
(2) Preparing a sodium alginate solution with the mass fraction of 2-3%, wherein the solvent is water;
(3) Mixing pheromone and ethanol according to the volume ratio of 1-2.5, then adding an ethanol solution of the pheromone into a sodium alginate solution, wherein the volume ratio of the ethanol solution of the pheromone to the sodium alginate solution is 1;
(4) And (2) dropwise adding sodium alginate emulsion containing pheromone into the multivalent cation solution obtained in the step (1), solidifying the gel to form gel ball particles, filtering out the particles, cleaning and drying to obtain the cat face pheromone gel balls.
2. The method of claim 1, wherein said pheromone composition comprises: one or more of methyl laurate, methyl myristate, methyl palmitate, methyl oleate, methyl linoleate and dimethyl sebacate.
3. The method of claim 2, wherein the pheromone is a mixture of one or more of methyl linoleate, methyl myristate, methyl laurate.
4. The method of claim 1, wherein in step (1), the multivalent cation solution is a calcium chloride solution.
5. The method of claim 1, wherein in step (1), the mass fraction of the multivalent cation solution is between 4.3 and 5.5%.
6. The process according to claim 1, wherein in step (2), the mass fraction of the sodium alginate solution is 2%.
7. The method of claim 1, wherein in step (3), the volume ratio of pheromone to ethanol is 1; the volume ratio of the ethanol solution of pheromone to the sodium alginate solution was 1.
8. The method as set forth in claim 1, wherein in the step (4), the dropping may be performed using syringes or droppers of different sizes to obtain gel balls having a particle size of 2 to 12mm.
9. Feline facial pheromone gel beads prepared according to the method of any one of claims 1 to 8.
10. The feline facial pheromone gel sphere of claim 9, wherein the feline facial pheromone gel sphere is spherical or irregularly ellipsoidal and the particle size of the gel sphere particles is from 2 to 12mm.
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