An old dog and cat joint maintenance nutritional supplement containing deep sea fish oil microcapsules and herbal essence and a preparation method thereof

Abstract

The application relates to the technical field of nutritional supplements, and discloses an old dog and cat joint maintenance nutritional supplement containing deep-sea fish oil microcapsules and herbal essence, which comprises the following components in proportion by weight: A component deep-sea fish oil microcapsules, 10-30%; B component herbal essence, 5-15%; C component matrix forming agent, 40-60%; D component synergistic solubilizer, 1-5%; and E component melting rheological modifier, 5-15%. The deep-sea fish oil microcapsules of the A component are completely wrapped in a composite matrix formed by the C component and the E component, and the nutritional supplement is in the form of particles. By introducing the melting rheological modifier and a low-temperature and low-shear melting wrapping process, the structure of the fish oil microcapsules can be protected, the fish oil microcapsules and the herbal essence can be doubly isolated by the composite matrix, the destruction of the fish oil microcapsules caused by the moisture absorption characteristics of the herbal essence can be avoided, the fish oil fishy smell and the herbal essence bitter taste can be covered, the product stability and palatability can be improved, the long-term taking demand of the old dogs and cats can be met, and the continuous effectiveness of the joint maintenance components can be ensured.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of nutritional supplements, in particular to an old dog and cat joint maintenance nutritional supplement containing deep sea fish oil microcapsules and herbal essence and a preparation method thereof. BACKGROUND

[0002] As the age increases, the joint cartilage of old dogs and cats is prone to degeneration and wear, causing joint discomfort, so joint maintenance nutritional supplements have become an important product to ensure the quality of life in their old age. Such supplements usually need to have anti-inflammatory and cartilage repair functions, and the industry often chooses fish oil and herbal essence as the core functional ingredients to meet the joint health needs of old dogs and cats.

[0003] In the prior art, to achieve the above functions, fish oil (usually made into microcapsules to reduce oxidation) and herbal essence with anti-inflammatory and repair functions are physically blended, and then a matrix forming agent is added to form a powder or granular product; the processing process relies on conventional processes such as dry granulation and wet granulation, and the components are simply combined, without designing an adaptive process for the differences in characteristics of fish oil microcapsules and herbal essence.

[0004] In the prior art, since herbal essence generally has hygroscopicity, it easily adsorbs trace amounts of moisture in the environment in the physical blending system, thereby damaging the capsule wall structure of fish oil microcapsules, causing fish oil to be exposed and oxidize and spoil, not only producing a pungent odor affecting animal palatability, but also reducing the efficacy of fish oil, making it difficult to ensure the stability of the supplement during storage and use, and unable to provide reliable joint maintenance effects for old dogs and cats for a long time. SUMMARY

[0005] To overcome the shortcomings of the prior art, the present application provides an old dog and cat joint maintenance nutritional supplement containing deep sea fish oil microcapsules and herbal essence and a preparation method thereof, which solves the problems of incompatibility, poor stability and low bioavailability of old dog and cat joint maintenance nutritional supplements.

[0006] To achieve the above purpose, the present application is implemented by the following technical scheme: an old dog and cat joint maintenance nutritional supplement containing deep sea fish oil microcapsules and herbal essence, comprising the following components by weight ratio:

[0007] A component deep sea fish oil microcapsules, 10-30%;

[0008] B component herbal essence, 5-15%; the B component is selected from at least one of herbal extracts with anti-inflammatory and cartilage repair functions;

[0009] C component matrix forming agent, 40-60%; the C component is polyethylene glycol 6000;

[0010] Group D is a synergistic solubilizer, 1-5%; the D group is phosphatidylcholine;

[0011] Group E is a melt rheology modifier, 5-15%; the E group is selected from at least one of poloxamer 188, sorbitan monostearate;

[0012] Wherein, the deep sea fish oil microcapsule of A component is completely included in the complex matrix formed by C component and E component, B component and D component are dispersed in the complex matrix in the form of amorphous solid dispersion, and the nutritional supplement is in granular form.

[0013] Preferably, the B component is selected from at least one of curcumin, frankincense extract, radix scutellariae extract, eucommia extract.

[0014] Preferably, in the A component, the effective component of the deep sea fish oil microcapsule is Omega-3 unsaturated fatty acid, and the content of Omega-3 unsaturated fatty acid is not less than 30% of the total weight of the microcapsule; the embedding rate of the deep sea fish oil microcapsule is not less than 90%.

[0015] Preferably, in the A component, the wall material of the deep sea fish oil microcapsule is selected from at least one of gum arabic and malt dextrin.

[0016] The particle size of the deep sea fish oil microcapsule is 50-200μm.

[0017] Preferably, in the A component, the deep sea fish oil is derived from at least one of sardines, mackerels and anchovies.

[0018] The weight ratio of eicosapentaenoic acid to docosahexaenoic acid in Omega-3 unsaturated fatty acid in the deep sea fish oil is 1.2-1.8:1.

[0019] A preparation method of an old dog and cat joint maintenance nutritional supplement of deep sea fish oil microcapsule and herbal essence, comprising the following steps:

[0020] Step S1, homogeneous premixing

[0021] The powders of A component, B component, C component, D component and E component are put into a V-type mixer for dry premixing to obtain a homogeneous powder to be processed;

[0022] Step S2, low-temperature and low-shear melt inclusion

[0023] The homogeneous powder to be processed obtained in step S1 is continuously fed into a twin-screw extruder or a hot melt granulator through a loss weight feeder, the heating temperature of the equipment barrel is controlled to be 55-65℃, and the screw rotation speed is controlled to be 50-100rpm, so that the C component and the E component are melted to form a melt matrix, at the same time, the B component and the D component are dispersed in the melt matrix to form an amorphous solid dispersion, and the A component is completely included in the melt matrix to obtain an extrudate.

[0024] Step S3, cooling forming

[0025] The extrudate obtained in step S2 is cooled to room temperature by a cooling roller or an air-cooled conveyor belt, the molten matrix is solidified, and then the solidified material is sequentially crushed and granulated to obtain a granular nutritional supplement.

[0026] Preferably, in step S1, the mixing speed of the V-type mixer is 15-30 rpm, and the mixing time is 10-20 minutes; the ambient temperature of the dry premixing process is controlled at 20-25 DEG C, and the relative humidity of the environment is controlled at 30-40%.

[0027] Preferably, in step S2, when a double-screw extruder is used, the barrel of the double-screw extruder is controlled at three temperatures, and the three temperatures are 55-58 DEG C, 58-62 DEG C and 62-65 DEG C in sequence; the feeding rate of the double-screw extruder is 10-15 kg / h.

[0028] Preferably, in step S2, when a hot melt granulator is used, the stirring paddle speed of the hot melt granulator is 40-80 rpm, and the cutter speed is 100-200 rpm; the residence time of the material in the hot melt granulator is 2-5 minutes.

[0029] Preferably, in step S3, when a cooling roller is used, the surface temperature of the cooling roller is controlled at 15-25 DEG C;

[0030] When an air-cooled conveyor belt is used, the air speed of the air-cooled conveyor belt is 1-3 m / s;

[0031] The sieving screen with a pore size of 1.0-2.0 mm is used for the granulation treatment, and the particle size of the finally obtained granules is 100-800 μm;

[0032] The crushing speed during the crushing process is 2000-3000 rpm.

[0033] The present application provides a kind of containing deep sea fish oil microcapsule and herbal essence of old dog cat joint maintenance nutritional supplement and its preparation method.There are following beneficial effects:

[0034] 1, the present application introduces melting rheological modifier and low-temperature low-shear melt inclusion process, which can protect the structure of fish oil microcapsule, form double isolation of fish oil microcapsule and herbal essence using composite matrix, avoid the damage of fish oil microcapsule caused by the moisture absorption characteristics of herbal essence, and cover up the fishy smell of fish oil and the bitter taste of herbal essence, improve the stability and palatability of product, meet the long-term use requirement of old dog cat, and guarantee the sustained effectiveness of joint maintenance ingredients.

[0035] 2、The present application disperses the herbal essence and the synergistic solubilizer in the form of amorphous solid dispersion in the molten matrix, combines the self-emulsifying properties of fish oil, forms a synergistic absorption microenvironment in the digestive tract, promotes the dissolution and transmembrane absorption of the herbal essence, realizes the synergistic effect of fish oil and herbal essence in joint maintenance efficacy, and is more suitable for the physiological characteristics of weak digestive and absorptive capacity of old dogs and cats.

[0036] 3、The present application adopts one-pot melt-inclusion process, without step-by-step processing of fish oil microcapsules and herbal essence, simplifies the production process, and through precise control of process parameters, ensures uniform dispersion of each component in the product, avoids local insufficient efficacy caused by component aggregation or uneven distribution, improves product quality consistency, and reduces the difficulty of large-scale production. BRIEF DESCRIPTION OF DRAWINGS

[0037] Figure 1 The preparation flowchart of the present application. DETAILED DESCRIPTION

[0038] The technical solutions in the embodiments of the present application will be described in detail below with reference to the drawings of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0039] For the convenience of understanding and making clear Figure 1 the correspondence between each step and the embodiments of the present specification, the purposes, preferred parameter ranges and characterization / quality control methods that can be used for each step S1, S2 and S3 in the present application will be described in detail. Figure 1 S1 (homogeneous premixing): After weighing the five components A, B, C, D and E according to the ratio, put them into a V-type mixer for dry premixing. The premixing parameters are as follows: mixing speed 15-30 rpm, mixing time 10-20 min, environmental temperature 20-25℃, and environmental relative humidity 30-40%. The purpose of this step is to ensure uniform distribution of the powder, reduce local overload or aggregation in the subsequent melting process, thereby protecting the microcapsule structure of component A and creating conditions for uniform melt-inclusion in S2.

[0040]

[0041] ​S2 (low temperature and low shear melt inclusion): the premix obtained in S1 is continuously fed into a twin-screw extruder or a hot melt granulator through a loss-in-weight feeder for melt inclusion, the twin-screw extruder is preferably controlled at three temperatures, and the three temperature examples are 55-58℃, 58-62℃ and 62-65℃ in turn; the screw rotation speed example is 50-100 rpm; the feeding rate example is 10-15 kg / h, when the hot melt granulator is used, the stirring paddle rotation speed example is 40-80 rpm, the cutter rotation speed is 100-200 rpm, and the material residence time example is 2-5 min, this step ensures the integrity of the microcapsules under the condition of forming a continuous matrix of C and E, and B and D are dispersed to form an amorphous solid dispersion (ASD), achieving the synergistic purpose of overall inclusion and solubilization / masking, and the quality control can include: microcapsule integrity / breakage rate detection, ASD verification, extrudate appearance and particle size detection, etc.

[0042] S3 (cooling molding and granulation): the extrudate is rapidly and uniformly cooled by a cooling roller or an air-cooled conveyor belt, and after cooling, it is crushed and sieved, and the crushing rotation speed example is 2000-3000 rpm, this step is used to solidify the molten matrix and obtain granules that can be commercialized, and the release / quality evaluation items can use: free fish oil content / microcapsule breakage rate, accelerated stability, in vitro dissolution and palatability test, etc.

[0043] The present application provides an old dog and cat joint maintenance nutritional supplement containing deep sea fish oil microcapsules and herbal essence and a preparation method thereof, specifically comprising:

[0044] I. Raw material part

[0045] The following raw materials are industrial grade or food grade, and meet the safety standards of old dog and cat nutritional supplements, and the specific information is as follows:

[0046] A component: the core effective component of deep sea fish oil microcapsules is Omega-3 unsaturated fatty acid (including eicosapentaenoic acid EPA and docosahexaenoic acid DHA), and the capsule wall material is selected from one or a mixture of two of gum arabic and malt dextrin; wherein the content of Omega-3 unsaturated fatty acid is not less than 30% of the total weight of the microcapsule, the weight ratio of EPA to DHA is 1.2-1.8:1, the particle size of the microcapsule is controlled in 50-200 μm, and the fish oil embedding rate is not less than 90%; the fish oil raw material is derived from at least one of sardines, mackerels and anchovies, and is treated by low temperature pressing and molecular distillation purification, and the peroxide value is ≤5 meq / kg.

[0047] B component: the herbal essence is selected from one or more of curcumin, boswellia extract, scutellaria extract, eucommia extract; wherein, the purity of curcumin is ≥95% (determined by high performance liquid chromatography HPLC), the content of boswellic acid in boswellia extract is ≥60%, the content of baicalin in scutellaria extract is ≥80%, and the content of chlorogenic acid in eucommia extract is ≥5%; all herbal essences are treated by ultrafine grinding, the particle size is ≤10 μm, and the water content is ≤5%.

[0048] C component: the matrix forming agent is polyethylene glycol 6000, the melting point is 56-63℃, the molecular weight distribution is uniform (the ratio of weight average molecular weight to number average molecular weight is ≤1.05), the ignition residue is ≤0.1%, and the water content is ≤0.2%, which meets the food-grade carrier standard.

[0049] D component: the synergistic solubilizer is phosphatidylcholine, which is derived from soybean or egg yolk, the purity of phosphatidylcholine is ≥90% (determined by thin layer chromatography TLC), the acid value is ≤20 mgKOH / g, the water content is ≤1.0%, and there is no solvent residue (such as ethanol, acetone).

[0050] E component: the melt rheology modifier is selected from one or a mixture of poloxamer 188 and sorbitan monostearate; wherein, the melting point of poloxamer 188 is 52-56℃, the hydroxyl value is 56-68 mgKOH / g, and the cloud point is ≥65℃ (1% aqueous solution); the melting point of sorbitan monostearate is 54-58℃, the acid value is ≤8 mgKOH / g, and the saponification value is 140-160 mgKOH / g.

[0051] The sources and specifications of the main raw materials and reagents used in the following examples and comparative examples are as follows, and the reagents not specifically described are commercially available analytical pure or higher grade products.

[0052] The deep sea fish oil microcapsule, the core effective component of which is deep sea fish oil from at least one of sardines, mackerels and anchovies, is treated by low-temperature pressing and molecular distillation purification, and has a peroxide value of ≤5 meq / kg, mainly contains Omega-3 unsaturated fatty acids, including eicosapentaenoic acid (EPA, CAS 10417-94-4) and docosahexaenoic acid (DHA, CAS 6217-54-5), wherein the content of Omega-3 unsaturated fatty acids is not less than 30% of the total weight of the microcapsule, and the weight ratio of EPA to DHA is 1.2-1.8:1; the microcapsule wall material is selected from one or a mixture of both of gum arabic or malt dextrin, the gum arabic is a natural high molecular polysaccharide (CAS 9000-01-5), the repeating unit mainly contains D-galactose, L-arabinose, L-rhamnose and D-glucuronic acid, and the weight average molecular weight ranges from 200000 to 300000 Da, and the water content is ≤15%; the malt dextrin is a starch hydrolysis product (CAS 9050-36-6), the dextrose equivalent value (DE value) ranges from 4 to 7, the weight average molecular weight ranges from 1000 to 3000 Da, the molecular weight distribution (ratio of weight average molecular weight to number average molecular weight) is ≤1.5, and the water content is ≤8%; the deep sea fish oil microcapsule is a non-commercial material, the particle size is controlled in the range of 50-200 μm, and the fish oil embedding rate is not less than 90%, and the specific preparation process is shown in the following preparation example.

[0053] The herbal essence is selected from one or a mixture of more than one of curcumin, frankincense extract, scute extract and eucommia extract, wherein the curcumin (CAS 458-37-7) has a chemical name of 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, a molecular structure containing two phenolic hydroxyl groups, two methoxy groups and a conjugated dienone structure, a purity of ≥95% (determined by high performance liquid chromatography HPLC), a water content of ≤5%, and a particle size of ≤10 μm; the core active component of the frankincense extract is boswellic acid (CAS 89957-94-0), which is a pentacyclic triterpenoid compound, the boswellic acid content in the extract is ≥60% (determined by high performance liquid chromatography HPLC), the water content is ≤5%, and the particle size is ≤10 μm; the core active component of the scute extract is baicalin (CAS 21967-41-9), which has a chemical name of 5,6-dihydroxy-7-(β-D-glucuronosyl)flavone, a molecular structure containing two phenolic hydroxyl groups, one glucuronic acid group and a flavone nucleus, the baicalin content in the extract is ≥80% (determined by high performance liquid chromatography HPLC), the water content is ≤5%, and the particle size is ≤10 μm; and the core active component of the eucommia extract is chlorogenic acid (CAS 327-97-9), which has a chemical name of 3-O-coffeoylquinic acid, a molecular structure containing a caffeoyl group and a quinic acid skeleton, the chlorogenic acid content in the extract is ≥5% (determined by high performance liquid chromatography HPLC), the water content is ≤5%, and the particle size is ≤10 μm.

[0054] The matrix forming agent is polyethylene glycol 6000 (CAS 25322-68-3), the chemical name is polyoxyethylene glycol, the molecular repeating unit is -(OCH2CH2)-, the average molecular weight range is 5500-7500 Da, the molecular weight distribution (ratio of weight average molecular weight to number average molecular weight) is ≤1.05, the melting point is 56-63℃, the ignition residue is ≤0.1%, the moisture content is ≤0.2%, which meets the food-grade carrier standard.

[0055] The synergistic solubilizer is phosphatidylcholine (CAS 8002-43-5), which is derived from soybean or egg yolk and belongs to phospholipid compounds. The molecular structure contains a phosphocholine polar head and two fatty acid hydrophobic chains. The purity is ≥90% (determined by thin layer chromatography TLC), the acid value is ≤20 mgKOH / g, the moisture content is ≤1.0%, and there is no ethanol, acetone and other solvent residues.

[0056] The melt rheology modifier is selected from one or a mixture of poloxamer 188 or sorbitan monostearate. Poloxamer 188 (CAS 9003-11-6) has a chemical name of polyoxyethylene polyoxypropylene ether block copolymer, a molecular structure containing polyoxyethylene segments (-(OCH2CH2)-) and polyoxypropylene segments (-(OCH(CH3)CH2)-), an average molecular weight range of 7680-9510 Da, a melting point of 52-56℃, a hydroxyl value of 56-68 mgKOH / g, and a 1% aqueous solution cloud point ≥65℃. Sorbitan monostearate (CAS 1338-41-6) has a chemical name of sorbitan monostearate, a molecular structure containing a sorbitan skeleton and a stearic acid hydrophobic chain, a melting point of 54-58℃, an acid value of ≤8 mgKOH / g, and a saponification value of 140-160 mgKOH / g, which meets the food-grade additive standard.

[0057] II. Preparation Example (Preparation of Deep Sea Fish Oil Microcapsules)

[0058] Preparation Example 1: Deep Sea Fish Oil Microcapsules with Acacia Capsule Wall

[0059] Weigh by weight: 30 parts of deep sea fish oil, 15 parts of acacia gum, 5 parts of malt dextrin, and 50 parts of deionized water;

[0060] Add acacia gum and malt dextrin to deionized water and stir at 50℃ for 30 minutes until completely dissolved to form an aqueous phase;

[0061] Slowly add deep sea fish oil to the aqueous phase and high-speed shear at 2000 rpm for 15 minutes to form a primary emulsion;

[0062] Pass the primary emulsion through a high-pressure homogenizer (pressure 30 MPa) for 3 times to obtain a nanoscale emulsion;

[0063] The nanoscale emulsion is sent into a spray dryer, the inlet air temperature is controlled at 180℃, the outlet air temperature is controlled at 80℃, and the feeding rate is controlled at 15 mL / min. After drying, the powder is collected, and the deep sea fish oil microcapsules are obtained. The particle size of the microcapsules is 80-120 μm, the Omega-3 content is 32%, and the embedding rate is 92%.

[0064] Preparation Example 2: Deep sea fish oil microcapsules with maltodextrin as the capsule wall

[0065] The deep sea fish oil, the maltodextrin, and the deionized water are weighed according to the weight ratio of 25:20:55;

[0066] The maltodextrin is added to the deionized water, and stirred at 45℃ for 40 minutes until completely dissolved to form the water phase;

[0067] The subsequent steps (high-speed shearing, high-pressure homogenization, and spray drying) are consistent with those in Preparation Example 1, and only the feeding rate of the spray drying is adjusted to 12 mL / min.

[0068] The particle size of the obtained deep sea fish oil microcapsules is 50-80 μm, the Omega-3 content is 28%, and the embedding rate is 90%.

[0069] Preparation Example 3: Deep sea fish oil microcapsules with arable gum-maltodextrin mixed capsule wall

[0070] The deep sea fish oil, the arable gum, the maltodextrin, and the deionized water are weighed according to the weight ratio of 35:10:10:45;

[0071] The arable gum and the maltodextrin are added to the deionized water, and stirred at 55℃ for 25 minutes until completely dissolved to form the water phase;

[0072] The subsequent steps (high-speed shearing, high-pressure homogenization, and spray drying) are consistent with those in Preparation Example 1, and only the high-pressure homogenization pressure is adjusted to 35 MPa.

[0073] The particle size of the obtained deep sea fish oil microcapsules is 120-200 μm, the Omega-3 content is 35%, and the embedding rate is 94%.

[0074] III. Examples (Preparation of the nutritional supplement of the present application)

[0075] The following examples all adopt the homogeneous premixing-low-temperature low-shearing melt inclusion-cooling molding process, and only the component ratio, the process parameter, or the raw material type is changed.

[0076] Example 1

[0077] The raw materials are weighed according to the weight ratio: the component A (the fish oil microcapsules of Preparation Example 1) 10%, the component B (curcumin) 15%, the component C (polyethylene glycol 6000) 60%, the component D (phosphatidylcholine) 5%, and the component E (poloxamer 188) 10%.

[0078] Homogeneous premixing: Put all the raw material powders into a V-type mixer, control the mixing speed at 15 rpm, the mixing time at 20 minutes, the ambient temperature at 20°C, and the ambient relative humidity at 30%, to obtain a homogeneous powder to be processed;

[0079] Low-temperature and low-shear melt inclusion: Put the homogeneous powder to be processed into a twin-screw extruder through a loss-on-weighing feeder (feeding rate 10 kg / h), control the barrel three-section temperature at 55°C, 58°C, and 62°C in turn, and the screw rotation speed at 50 rpm, to obtain an extrudate;

[0080] Cooling and forming: Cool the extrudate to room temperature through a cooling roller (surface temperature 15°C), then crush it through a crusher (rotation speed 2000 rpm) and sieve it through a 1.0 mm aperture screen, to obtain a granular nutritional supplement with a particle size of 100-300 μm.

[0081] Example 2

[0082] Weigh the raw materials according to the proportion by weight: A component (fish oil microcapsule of Preparation Example 2) 20%, B component (olibanum extract) 10%, C component (polyethylene glycol 6000) 52%, D component (phosphatidylcholine) 3%, and E component (sorbitan monostearate) 15% (Note: The proportion of E component is adjusted to the upper limit of 15% to verify the reasonableness of the content range).

[0083] Homogeneous premixing: V-type mixer speed 25 rpm, mixing time 15 minutes, ambient temperature 23°C, and ambient relative humidity 35%;

[0084] Low-temperature and low-shear melt inclusion: Use a hot-melt granulator, control the barrel temperature at 58-63°C, the stirring paddle rotation speed at 60 rpm, the cutter rotation speed at 150 rpm, and the material residence time at 3 minutes;

[0085] Cooling and forming: Cool through an air-cooled conveyor belt (air speed 2 m / s), crush through a crusher at a rotation speed of 2500 rpm, and sieve through a 1.5 mm aperture screen, to obtain a granular particle size of 300-500 μm.

[0086] Example 3

[0087] Weigh the raw materials according to the proportion by weight: A component (fish oil microcapsule of Preparation Example 3) 30%, B component (scute extract + eucommia extract, weight ratio 1:1) 8%, C component (polyethylene glycol 6000) 56%, D component (phosphatidylcholine) 1%, and E component (poloxamer 188 + sorbitan monostearate, weight ratio 2:1) 5%;

[0088] Homogeneous premixing: Put all the raw material powders into a V-type mixer, control the mixing speed at 30 rpm, the mixing time at 10 minutes, the ambient temperature at 25°C, and the ambient relative humidity at 40%, to obtain a homogeneous powder to be processed;

[0089] Low temperature and low shear melt-inclusion: the homogenous powder was fed into a twin-screw extruder by a loss-in-weight feeder (feeding rate 15 kg / h), the barrel temperature was controlled at 58℃, 62℃, 65℃, respectively, the screw speed was 100 rpm, and the extrudate was obtained;

[0090] Cooling and forming: the extrudate was cooled to room temperature by a cooling roller (surface temperature 25℃), then was crushed by a crusher (speed 3000 rpm) and sieved by a 2.0 mm mesh screen, and the granular nutritional supplement was obtained, with a particle size of 500-800 μm.

[0091] Example 4

[0092] The raw materials were weighed according to the proportion by weight: A component (fish oil microcapsule of Preparation Example 1) 15%, B component (curcumin + boswellia extract, weight ratio 3:2) 12%, C component (polyethylene glycol 6000) 55%, D component (phosphatidylcholine) 4%, E component (poloxamer 188) 14%;

[0093] Homogeneous premixing: V-type mixer speed 20 rpm, mixing time 18 minutes, ambient temperature 22℃, ambient relative humidity 33%;

[0094] Low temperature and low shear melt-inclusion: the barrel temperature of the hot melt granulator was 55-60℃, the stirring paddle speed was 40 rpm, the cutter speed was 100 rpm, and the material residence time was 5 minutes;

[0095] Cooling and forming: the air cooling conveyor belt speed was 1 m / s, the crusher speed was 2200 rpm, and the 1.2 mm mesh screen was used for sieving, and the granular particle size was 200-400 μm.

[0096] Example 5

[0097] The raw materials were weighed according to the proportion by weight: A component (fish oil microcapsule of Preparation Example 2) 25%, B component (eucommia extract) 8%, C component (polyethylene glycol 6000) 48%, D component (phosphatidylcholine) 2%, E component (sorbitan monostearate) 17%;

[0098] Homogeneous premixing: V-type mixer speed 28 rpm, mixing time 12 minutes, ambient temperature 24℃, ambient relative humidity 38%;

[0099] Low temperature and low shear melt-inclusion: the barrel temperature of the twin-screw extruder was 56℃, 60℃, 63℃, respectively, the screw speed was 75 rpm, and the feeding rate was 12 kg / h;

[0100] Cooling and forming: the cooling roller surface temperature was 20℃, the crusher speed was 2800 rpm, and the 1.8 mm mesh screen was used for sieving, and the granular particle size was 400-600 μm.

[0101] IV. Comparative Example (Contrast with the present invention, highlighting the advantages)

[0102] Comparative Example 1: Without E component (verify the necessity of E component)

[0103] Raw material formulation: A component (fish oil microcapsule of Preparation Example 1) 20%, B component (curcumin) 10%, C component (polyethylene glycol 6000) 60%, D component (phosphatidylcholine) 10% (without E component);

[0104] Preparation process: The homogeneous premixing step is consistent with Example 2; during melt inclusion, the screw speed of the twin-screw extruder needs to be increased to 200 rpm to push the material due to the extremely high viscosity of the system, and the barrel temperature is 58-63°C; the cooling molding step is consistent with Example 2.

[0105] Comparative Example 2: With E component but high speed (verify the necessity of low speed)

[0106] Raw material formulation: exactly the same as Example 2 (A component 20%, B component 10%, C component 50%, D component 3%, E component 17%);

[0107] Preparation process: The homogeneous premixing step is consistent with Example 2; during melt inclusion, the screw speed of the twin-screw extruder is increased to 150 rpm (exceeding the upper limit of 100 rpm of the present invention), and the barrel temperature is 58-63°C; the cooling molding step is consistent with Example 2.

[0108] Comparative Example 3: Physical blending process (verify the necessity of melt inclusion process)

[0109] Raw material formulation: exactly the same as Example 2;

[0110] Preparation process: all raw material powders are put into a V-type mixer and mixed for 30 minutes according to the premixing parameters of Example 2 (without melt inclusion step), directly obtaining a physical blending powder (not granular).

[0111] Comparative Example 4: Temperature below the lower limit (verify the necessity of temperature range)

[0112] Raw material formulation: exactly the same as Example 2;

[0113] Preparation process: The homogeneous premixing step is consistent with Example 2; during melt inclusion, the barrel temperature of the twin-screw extruder is controlled at 50-53°C (lower than the lower limit of 55°C of the present invention), and the screw speed is 75 rpm; due to insufficient melting of C and E components, the system is in block agglomeration and cannot form continuous extrudates, finally only obtaining a non-uniform powder-particle mixture.

[0114] Comparative Example 5: Temperature above the upper limit (verify the necessity of temperature range)

[0115] Raw material formulation: exactly the same as Example 2;

[0116] Preparation process: the homogeneous premixing step is consistent with Example 2; during melt inclusion, the barrel temperature of the twin-screw extruder is controlled at 70-73°C (higher than the upper limit of 65°C in the present application), and the screw rotation speed is 75 rpm; the cooling molding step is consistent with Example 2.

[0117] Comparative Example 6: rotation speed lower than the lower limit (verify the necessity of the rotation speed range)

[0118] Raw material formulation: exactly the same as Example 2;

[0119] Preparation process: the homogeneous premixing step is consistent with Example 2; during melt inclusion, the screw rotation speed of the twin-screw extruder is controlled at 40 rpm (lower than the lower limit of 50 rpm in the present application), and the barrel temperature is 58-63°C; the material stays in the barrel for too long (up to 8 minutes), and the B and D components are not evenly dispersed, with obvious agglomeration spots of the B component in the final granules.

[0120] Comparative Example 7: without D component (verify the effect of D component on bioavailability)

[0121] Raw material formulation: A component (fish oil microcapsules prepared in Preparation Example 2) 20%, B component (olibanum extract) 10%, C component (polyethylene glycol 6000) 53%, E component (sorbitan monostearate) 17% (without D component);

[0122] Preparation process: exactly the same as Example 2.

[0123] V. Test Examples

[0124] Test Example 1: microcapsule integrity test (verify the complete inclusion feature)

[0125] Test samples: granules of Examples 1-5, Comparative Examples 1-2, and Comparative Example 5;

[0126] Test method:

[0127] Electron microscope observation: take granules of each sample, fracture them in liquid nitrogen, and observe the cross-section by scanning electron microscope (SEM), and calculate the proportion of complete microcapsules (randomly select 100 microcapsules, the number of complete microcapsules / the total number of microcapsules x 100%);

[0128] Free fish oil detection: weigh 10g of sample, add 50mL of n-hexane, shake and extract for 30 minutes, centrifuge to take the supernatant, detect the free fish oil content by gas chromatography (GC), and calculate the microcapsule rupture rate (free fish oil content / total fish oil content in the sample x 100%);

[0129] Test results:

[0130]

[0131] Conclusion: The microcapsule integrity of Examples 1-5 is significantly better than the comparative examples, which proves that the E component + low rotation speed + suitable temperature can effectively protect the microcapsule of the A component; Comparative Example 1 (without E), Comparative Example 2 (high rotation speed), and Comparative Example 5 (high temperature) all deviate from the range of the present application due to the process parameters, resulting in a large number of microcapsule ruptures.

[0132] Test Example 2: ASD state test (verify the characteristics of amorphous solid dispersion)

[0133] Test samples: granules of Examples 1-5 and Comparative Example 3 (physical blending);

[0134] Test method:

[0135] DSC test: Take 5 mg of each sample, and record the differential scanning calorimetry curve under the condition of nitrogen atmosphere and at a rate of 10℃ / min from 25℃ to 200℃, and observe the crystalline melting peak of the B component (the crystalline melting peak of curcumin is about 183℃, and the crystalline melting peak of boswellia extract is about 175℃);

[0136] PXRD test: Take each sample, and scan in the range of 2θ = 5-40° by using an X-ray diffractometer (Cu target, λ = 1.54Å), and observe the characteristic crystalline peak of the B component (the characteristic peak of curcumin is 2θ = 8.8°, 17.7°, and the characteristic peak of boswellia extract is 2θ = 10.2°, 19.5°);

[0137] Test results:

[0138] In the DSC curve of Examples 1-5, the crystalline melting peak of the B component does not appear; in the PXRD spectrum, there is no characteristic crystalline peak of the B component, and only an amorphous halo peak (2θ = 15-25°) is presented, which proves that the B component exists in the form of ASD;

[0139] In the DSC curve of Comparative Example 3 (physical blending), the crystalline melting peak of the B component is clearly present; in the PXRD spectrum, the characteristic crystalline peak of the B component is sharp and high in intensity, which proves that the B component exists in the crystalline state;

[0140] Conclusion: The melt inclusion process of the present application can convert the B component into ASD, while physical blending cannot achieve this, which lays a foundation for the improvement of bioavailability.

[0141] Test Example 3: Stability test (verify the advantage of high stability)

[0142] Test samples: granules of Examples 1-5, Comparative Examples 1-3, and Comparative Example 5;

[0143] Test condition: accelerated storage condition (40℃, relative humidity 75%), sample at 0 day, 30 days, 90 days, 180 days respectively for detection;

[0144] Test index:

[0145] Omega-3 oxidation index: anisidine value (AV) was detected according to the method of GB5009.281-2021;

[0146] Sensory evaluation: 10 professional evaluators scored the fishy smell intensity of the samples (1 point: no fishy smell, 5 points: extremely strong fishy smell);

[0147] Test results (180 days data):

[0148]

[0149] Conclusion: after 180 days of accelerated storage, the Omega-3 oxidation degree and fishy smell of examples 1-5 are low, and the stability is significantly better than that of the comparative examples; due to microcapsule rupture (1, 2, 5) or no inclusion protection (3), the fish oil is easy to oxidize and has a strong fishy smell.

[0150] Test example 4: bioavailability test (verify the advantage of high bioavailability)

[0151] Test sample: granules of examples 1-5, comparative example 3, and comparative example 7;

[0152] Test method: in vitro dissolution test, using simulated canine and feline intestinal fluid (pH=6.8, containing 0.5% sodium dodecyl sulfate), according to the dissolution test method (paddle method) of Chinese Pharmacopoeia 2020 edition, rotation speed 50 rpm, temperature 37℃, sample at 5 minutes, 15 minutes, 30 minutes, 60 minutes respectively, the dissolution amount of B component was detected by HPLC, and the cumulative dissolution rate was calculated;

[0153] Test results (60 minutes cumulative dissolution rate):

[0154]

[0155] Conclusion: the cumulative dissolution rate of B component of examples 1-5 is significantly higher than that of comparative example 3 (physical blending) and comparative example 7 (without D component), which proves that the self-emulsifying effect of ASD+D component+A component can greatly improve the solubility of B component, and thus improve the bioavailability; without D component, the dissolution rate decreases significantly, which proves that the synergistic solubilization effect of D component is indispensable.

[0156] Test example 5: palatability test (verify the advantage of excellent palatability)

[0157] Test sample: granules of examples 1-5 and comparative examples 1-3;

[0158] Test subjects: 10 old dogs (8-10 years old, 10-15 kg in weight), 10 old cats (7-9 years old, 3-5 kg in weight);

[0159] Test method: double-bowl selection method was adopted, two identical bowls were placed in front of each animal, 20 g of test sample was filled in each bowl, the intake amount of each sample within 1 hour was recorded, and the preference rate (intake amount of a certain sample / total intake amount of two samples x 100%) was calculated;

[0160] Test results (average preference rate of dogs and cats):

[0161]

[0162] Conclusion: the preference rates of dogs and cats of examples 1-5 are significantly higher than those of the comparative examples, which proves that the melt matrix of the present application can effectively mask the fishy smell of component A and the bitter taste of component B, and has excellent palatability; the comparative examples have obvious fishy smell / bitter taste due to microcapsule rupture or no inclusion, resulting in low acceptance of animals.

[0163] Although the embodiments of the present application have been shown and described, it can be understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present application, and the scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A nutritional supplement for joint care in senior dogs and cats containing deep-sea fish oil microcapsules and herbal extracts, characterized in that, It contains the following components by weight percentage: Component A: Deep-sea fish oil microcapsules, 10-30%; Component B is a herbal extract, 5-15%; Component B is selected from at least one of herbal extracts with anti-inflammatory and cartilage repair effects, and Component B is selected from at least one of curcumin, frankincense extract, scutellaria baicalensis extract, and eucommia ulmoides extract. Component C matrix forming agent, 40-60%; wherein component C is polyethylene glycol 6000; Component D is a co-solvent, 1-5%; Component D is phosphatidylcholine; Component E is a melt rheology modifier, 5-15%; Component E is selected from at least one of poloxamer 188 and sorbitan monostearate. In this component, the deep-sea fish oil microcapsules of component A are completely encapsulated in the composite matrix formed by components C and E, while components B and D are dispersed in the composite matrix in the form of amorphous solid dispersions, and the nutritional supplement is in granular form. The preparation method of the joint care nutritional supplement for senior dogs and cats containing deep-sea fish oil microcapsules and herbal extracts includes the following steps: Step S1: Homogeneous premixing Powders of components A, B, C, D, and E are put into a V-type mixer for dry premixing to obtain homogeneous powders to be processed. Step S2: Low-temperature, low-shear melt encapsulation The homogeneous powder to be processed obtained in step S1 is continuously fed into a twin-screw extruder through a loss-in-weight feeder. The barrel heating temperature is controlled at 55-65℃ and the screw speed is controlled at 50-100rpm, so that component C and component E melt to form a molten matrix. At the same time, component B and component D are dispersed in the molten matrix to form an amorphous solid dispersion. Component A is completely encapsulated in the molten matrix to obtain the extrudate. Step S3, Cooling and Molding The extrudate obtained in step S2 is cooled to room temperature by a cooling roller or an air-cooled conveyor belt to solidify the molten matrix. The solidified material is then crushed and granulated to obtain granular nutritional supplements.

2. The joint care nutritional supplement for senior dogs and cats containing deep-sea fish oil microcapsules and herbal extracts according to claim 1, characterized in that, In component A, the effective ingredient of the deep-sea fish oil microcapsules is Omega-3 unsaturated fatty acids, and the content of Omega-3 unsaturated fatty acids is not less than 30% of the total weight of the microcapsules; the encapsulation rate of the deep-sea fish oil microcapsules is not less than 90%.

3. The joint care nutritional supplement for senior dogs and cats containing deep-sea fish oil microcapsules and herbal extracts according to claim 1, characterized in that, In component A, the capsule wall material of the deep-sea fish oil microcapsules is selected from at least one of gum arabic and maltodextrin; The particle size of deep-sea fish oil microcapsules is 50-200 μm.

4. The joint care nutritional supplement for senior dogs and cats containing deep-sea fish oil microcapsules and herbal extracts according to claim 1, characterized in that, In component A, the deep-sea fish oil is derived from at least one of sardines, mackerel, and anchovies; The weight ratio of eicosapentaenoic acid to docosahexaenoic acid in the Omega-3 unsaturated fatty acids in deep-sea fish oil is 1.2-1.8:

1.

5. A nutritional supplement for joint care in senior dogs and cats containing deep-sea fish oil microcapsules and herbal extracts according to claim 1, characterized in that, In step S1, the mixing speed of the V-type mixer is 15-30 rpm and the mixing time is 10-20 minutes; the ambient temperature of the dry premixing process is controlled at 20-25℃ and the relative humidity is controlled at 30-40%.

6. A nutritional supplement for joint care in senior dogs and cats containing deep-sea fish oil microcapsules and herbal extracts according to claim 1, characterized in that, In step S2, when a twin-screw extruder is used, the barrel of the twin-screw extruder is controlled by three temperature sections, with the three temperature sections being 55-58℃, 58-62℃, and 62-65℃ respectively; the feeding rate of the twin-screw extruder is 10-15 kg / h.

7. A nutritional supplement for joint care in senior dogs and cats containing deep-sea fish oil microcapsules and herbal extracts according to claim 1, characterized in that, In step S3, when a cooling roller is used, the surface temperature of the cooling roller is controlled to be 15-25℃. When using an air-cooled conveyor belt, the air velocity of the air-cooled conveyor belt is 1-3 m / s; The granulation process uses a sieve with a pore size of 1.0-2.0 mm, and the final particle size is 100-800 μm. The grinding speed during the grinding process is 2000-3000 rpm.

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