An anti-inflammatory composition containing antimicrobial peptides and preparation method thereof

By using tachyplesinⅢ and modified gelatin solution in the anti-inflammatory composition, combined with the improved homogenization device, the low absorption rate and instability of the anti-inflammatory cream are solved, and antibacterial peptides are achieved dual performance and long-term stability of the product.

CN118717948BActive Publication Date: 2025-01-14李炜湉
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Patent Information

Application Number
CN202411039362.1
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2024-07-31
Publication Date
2025-01-14
Estimated Expiration
2044-07-31

AI Technical Summary

Technical Problem

The existing anti-inflammatory creams containing antimicrobial peptides have low absorption rate and are unstable, which easily leads to unstable efficacy due to oil-water separation. The lack of optimized structure of existing mixing equipment makes it difficult to achieve homogeneous treatment.

Method used

Using an anti-inflammatory composition containing tachyplesinⅢ, combined with modified gelatin solution and high and low temperature secondary homogenization technology, a stable phase is formed by the hydrophilic and hydrophobic groups of the modified gelatin solution, and homogenization is carried out using an improved homogenization device. Quality treatment ensures stable mixing of the aqueous phase, oil phase and emulsifier.

Benefits of technology

It improves the stability and activity of antimicrobial peptides, ensures the stability and homogeneity of the product under high and low temperature conditions, avoids the problems of oil-water separation and unstable efficacy, and improves product quality.

✦ Generated by Eureka AI based on patent content.

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Abstract

The invention relates to the technical field of biomedicine preparation, in particular to an anti-inflammatory composition containing antimicrobial peptides and a preparation method thereof. The invention creatively contains tachyplesin III antimicrobial peptides in the composition; the composition has excellent dual performances of cold resistance and high temperature resistance, can meet the needs of high and low temperature secondary homogenization, and has high activity of the antimicrobial peptides after homogenization; the introduction of modified gelatin solution can have a positive effect on the thermal stability of the product; the modified gelatin solution has hydrophilic groups and hydrophobic groups, can form a stable phase with an aqueous phase, an oil phase and an emulsifier, and the phase will not be stratified due to high and low temperature secondary homogenization; the high and low temperature secondary homogenization is adopted to solve the problem of insufficient dispersibility after adding antimicrobial peptides, artemisia annua extracts and medicinal porphyra extracts; a homogenization auxiliary mechanism is arranged in the inner cavity of a homogenization device to meet the requirement that the oil and water floating on the upper layer are better mixed therein, which can better meet the actual homogenization work requirements and has a positive effect on improving product quality.
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Description

Technical Field

[0001] The invention relates to the technical field of biomedicine preparation, in particular to an anti-inflammatory composition containing antimicrobial peptides and a preparation method thereof. Background Art

[0002] Antimicrobial peptides (AMPs) are a class of small molecule polypeptides with antimicrobial activity composed of 5-100 amino acid residues, which are encoded by specific genes of organisms and induced by external factors. They mainly come from plants, insects, amphibians, mammals, marine organisms, bacteria, viruses, etc. They are an important defense system in natural organisms. The antimicrobial activity of antimicrobial peptides is characterized by high selectivity, rapid bactericidal action, broad spectrum of action and difficulty in forming resistance, which makes them ideal candidates for the research and development of new antibiotics.

[0003] At present, five types of horseshoe crab antimicrobial peptides have been discovered, namely tachyplesin I, tachyplesin II, tachyplesin III, Polyphemusin I and Polyphemusin II. Among them, tachyplesin I is the most widely studied and used. When simulating the human gastric and intestinal environment and testing the biological activity of genetically engineered antimicrobial peptides, it was found that tachyplesin I is stable under conditions below 100°C and pH less than 10.3, and the cation concentration and solution polarity have a certain influence on the antimicrobial activity of tachyplesin I; when the concentration of tachyplesin I is greater than 80 mg / L and the action time is greater than 30 min, it exhibits a certain hemolytic activity; tachyplesin I exhibits high stability in simulated gastric juice, gastric mucosal homogenate and plasma systems, the chromatographic peak shape is basically unchanged, and there is almost no degradation effect.

[0004] Therefore, tachyplesin I has strong high temperature tolerance, is stable under acidic conditions, and has a certain ability to withstand degradation by proteases in the body. However, tachyplesin I is not stable enough under low temperature conditions and is easily affected by external factors such as temperature, pH, and mechanical forces, resulting in poor activity.

[0005] However, there are relatively few studies on tachyplesinⅡ, tachyplesinⅢ, PolyphemusinI and PolyphemusinⅡ.

[0006] The anti-inflammatory cream containing antimicrobial peptides in the prior art has the following problems: 1. The absorption rate is low, resulting in waste of raw materials; 2. Since the cream is formed by an aqueous phase, an oil phase and an emulsifier, the cream is easily unstable after long-term storage and easily loses its effectiveness due to oil-water separation; the main drug component is unevenly distributed in the cream, making the efficacy unstable.

[0007] The existing patent document with announcement number CN213643959U discloses a homogenizing device for the production of polypeptide drugs. The homogenizing treatment of drugs in the scheme and the prior art is carried out by stirring and mixing. However, it is difficult for the oil and water floating on the upper layer of the material to be fully mixed with the material at the bottom during the mixing, and thus it is difficult to achieve the homogenization requirement. The existing mixing components lack a suitable auxiliary structure for optimizing the mixing treatment.

[0008] To this end, the present invention provides an anti-inflammatory composition containing antimicrobial peptides and a preparation method for solving the above problems. Summary of the invention

[0009] The object of the present invention is to provide an anti-inflammatory composition containing antimicrobial peptides and a preparation method thereof, so as to solve the problems raised in the above background technology.

[0010] To achieve the above object, the present invention provides the following technical solution: an anti-inflammatory composition containing an antimicrobial peptide, comprising, by weight: 0.001-0.06 parts by weight of an antimicrobial peptide, 0.01-0.5 parts by weight of an Artemisia annua extract, 0.01-0.5 parts by weight of a medicinal porphyra extract, 15-17 parts by weight of a water-based auxiliary material, 15-18 parts by weight of an oil-based auxiliary material, 30-60 parts by weight of a modified gelatin solution, 0.6-1 parts by weight of carbomer, and 136-140 parts by weight of water, wherein the antimicrobial peptide is tachyplesin III,

[0011] The water-based auxiliary materials are composed of disodium ethylenediaminetetraacetate, ethylparaben, sorbitol and triethanolamine in a weight ratio of (0.01-0.02): (0.01-0.02): (10-15): (1.0-2.0) in sequence;

[0012] The oil-based auxiliary material includes glyceryl stearate, polyethylene glycol stearate, peregal, octadecyl alcohol, and hexadecanol, wherein the weight ratio is (6-8): (1-3): (1.5-3): (1.5-3): (1.5-3).

[0013] A method for preparing an anti-inflammatory composition containing an antimicrobial peptide comprises the following steps: firstly mixing water, disodium ethylenediaminetetraacetate and ethylparaben, adding the modified gelatin solution and carbomer under stirring, leaving overnight, filtering, adding sorbitol and triethanolamine to the filtrate under stirring rate of 20-30 r / min, continuing stirring for 5 minutes, and heating to 65-75° C. to obtain an aqueous phase;

[0014] Step 2: Mix the oil-based auxiliary materials at 70-80° C. and keep warm for 25-45 minutes to obtain an oil phase;

[0015] Step 3: mixing the antimicrobial peptide, the Artemisia annua extract and the medicinal phytomycetes extract in a mixer to obtain the main drug;

[0016] Step 4: Filter the oil phase and vacuum-absorb it into an emulsification tank, mix it with the water phase at 28-35 r / min, homogenize it once at 70-80°C at 2300-2800 r / min for 4-7 min through a homogenizer, add the main drug and homogenize it for a second time, and control it at 5-10°C and 2300-2800 r / min for 2-4 min under a cold water bath.

[0017] Preferably, the preparation method of modified gelatin includes: adding a surfactant sodium alkyl sulfate and deionized water, stirring and heating to 50°C, and after complete dissolution, adjusting the reaction pH to 8.0-9.0, adding gelatin, continuing to stir until the gelatin is completely dissolved, adding monoepoxy-terminated polysiloxane, reacting for 24 hours until the primary amine content no longer changes, stopping stirring and heating, and obtaining a modified gelatin solution.

[0018] Preferably, the preparation method of the modified gelatin comprises, in parts by mass: 0.1-0.5 parts of sodium alkyl sulfate, 90-105 parts of deionized water, 3-6 g of gelatin, and the amount of monoepoxy-terminated polysiloxane used is 0.8 times the molar amount of primary amino groups in the gelatin molecule.

[0019] Preferably, the homogenizing device includes a homogenizing device body, a rotation control motor, a connecting shaft and a homogenizing auxiliary mechanism; a rotation control motor is provided on the homogenizing device body, one end of the rotation control motor is connected to the connecting shaft, the connecting shaft extends into the inner cavity of the homogenizing device body, and the connecting shaft is connected to the homogenizing auxiliary mechanism.

[0020] Preferably, the homogenization auxiliary mechanism comprises a fixed cylinder, a delivery pipe, a control pump body, a rotating connector, a movable sleeve, a connecting strip, an immersion pipe network, a homogenization stirring rod, a first auxiliary hole, a connecting vertical rod, a second auxiliary hole and an auxiliary component; one end of the fixed cylinder is fixedly arranged on the top of the inner cavity of the homogenization device body, and the other end of the fixed cylinder is provided with a rotating connector, one side of the fixed cylinder is connected with a delivery pipe, the delivery pipe is connected to the control pump body, and the control pump body is arranged on the homogenization device body, the other end of the rotating connector is connected to one end of the movable sleeve, the inner side wall of the bottom end of the movable sleeve is equidistantly fixed with connecting strips, the other end of the connecting strip is fixedly connected to the side wall of the connecting shaft, the movable sleeve is provided with an immersion pipe network, the homogenization stirring rod is equidistantly fixed on the side wall of the movable sleeve, the homogenization stirring rod is equidistantly provided with a first auxiliary hole, the other end of the homogenization stirring rod is arranged on the connecting vertical rod, the second auxiliary hole is equidistantly provided on the connecting vertical rod, and the inner side wall of the movable sleeve is provided with an auxiliary component.

[0021] Preferably, the homogenizing stirring rod is hollow and is connected to the movable sleeve.

[0022] Preferably, the connecting vertical rod is hollow and connected to the homogenizing stirring rod, and the homogenizing stirring rod is perpendicular to the connecting vertical rod.

[0023] Preferably, the auxiliary component includes a cut-off ring body and a drainage auxiliary slope; the cut-off ring body is fixedly arranged on the inner wall of the movable sleeve at equal distances, and the upper end surface of the cut-off ring body is arranged as the drainage auxiliary slope.

[0024] Preferably, the drainage auxiliary slope is arranged in a ring shape, and the drainage auxiliary slope corresponds to the setting position of the pipe opening of the homogenizing stirring rod; the inner diameter of the intercepting ring body gradually decreases from top to bottom.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] On the one hand, the present invention creatively contains tachyplesin III antimicrobial peptide, which has excellent dual performance of cold resistance and high temperature resistance, can meet the needs of high and low temperature secondary homogenization, and the antimicrobial peptide activity after homogenization is relatively high;

[0027] On the other hand, the invention creatively introduces the modified gelatin solution, which can have a positive effect on the thermal stability of the product. The modified gelatin solution has hydrophilic groups and hydrophobic groups, and can form a stable phase with the water phase, the oil phase and the emulsifier, and the phase will not be subjected to high and low temperature secondary homogenization and cause stratification;

[0028] Furthermore, the present invention creatively adopts high and low temperature secondary homogenization to solve the problem of insufficient dispersibility after adding antimicrobial peptides, Artemisia annua extract and medicinal porphyra extract, and utilizes a homogenizing device to further solve the problem of forming a stable phase between the water phase, the oil phase and the emulsifier, and the phase will not be stratified due to high and low temperature secondary homogenization; and by arranging a corresponding homogenizing device in the preparation method, by arranging a homogenizing auxiliary mechanism in the inner cavity of the homogenizing device, the oil and water floating on the upper layer can be better mixed therein, which can better meet the actual homogenization work requirements and has a positive effect on improving product quality. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 This is a tiling state diagram of a product according to an embodiment of the present invention;

[0030] Figure 2 This is a diagram showing the product of comparative example 1 of the present invention in a flattened state;

[0031] Figure 3 This is a diagram showing the flattening state of the product of Comparative Example 2 of the present invention;

[0032] Figure 4 This is a diagram showing the flattening state of the product of Comparative Example 3 of the present invention;

[0033] Figure 5 A top view of the structural connection of the homogenizing device of the present invention;

[0034] Figure 6 For the present invention Figure 5 A magnified schematic diagram of the structural connection at center A;

[0035] Figure 7 It is a schematic diagram of the front side of the homogenizing device structure connection of the present invention;

[0036] Figure 8 It is a schematic diagram of the connection between the rotating shaft and the homogenization auxiliary mechanism and the auxiliary component structure of the present invention;

[0037] Fig. 9 For the present invention Figure 8 A magnified schematic diagram of the structural connection at B in the middle;

[0038] Fig.10 It is a schematic diagram of the connection between the homogenization auxiliary mechanism and the local structure of the auxiliary component of the present invention;

[0039] Fig.11 For the present invention Fig.10 A magnified schematic diagram of the structural connection at C in the middle;

[0040] Fig.12 For the present invention Fig.10 Enlarged schematic diagram of the structural connection at point D in the middle.

[0041] In the figure: a homogenizing device body 1, a rotating control motor 2, a connecting shaft 3, a fixed cylinder 401, a delivery pipe 402, a control pump body 403, a rotating connecting piece 404, a movable sleeve 405, a connecting strip 406, an immersion pipe network 407, a homogenizing stirring rod 408, a first auxiliary hole 409, a connecting vertical rod 410, a second auxiliary hole 411, a intercepting ring 501, and a drainage auxiliary slope 502. DETAILED DESCRIPTION

[0042] The technical solutions in the embodiments of the present invention are described clearly and completely below. The embodiments of the present invention and all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present invention.

[0043] In order to better understand the present invention, a specific embodiment is used for illustration. It is worth emphasizing that the effect of this embodiment is no substantially different from the various embodiments within the protection scope of the present invention, including the respective reagents and the content ratio of the reagents, and all can achieve the effects described in the present invention and solve the above-mentioned problems. Other combinations are not described here.

[0044] Embodiment: An anti-inflammatory composition containing an antimicrobial peptide, comprising, by weight: 0.001-0.06 parts of antimicrobial peptide, 0.01-0.5 parts of Artemisia annua extract, 0.01-0.5 parts of medicinal porphyra extract, 15-17 parts of water-based excipients, 15-18 parts of oil-based excipients, 30-60 parts of modified gelatin solution, 0.6-1 parts of carbomer, and 136-140 parts of water, wherein the antimicrobial peptide is tachyplesin III.

[0045] The water-based auxiliary materials are composed of disodium ethylenediaminetetraacetic acid, ethylparaben, sorbitol and triethanolamine in the weight ratio of (0.01-0.02): (0.01-0.02): (10-15): (1.0-2.0);

[0046] The oil-based auxiliary materials include glyceryl stearate, polyethylene glycol stearate, peregal, octadecyl alcohol, and hexadecanol, wherein the weight ratio is (6-8): (1-3): (1.5-3): (1.5-3): (1.5-3).

[0047] A method for preparing an anti-inflammatory composition containing an antimicrobial peptide comprises the following steps: firstly mixing water, disodium ethylenediaminetetraacetate and ethylparaben, adding a modified gelatin solution and carbomer under stirring, leaving the mixture overnight, filtering, adding sorbitol and triethanolamine to the filtrate under stirring at a rate of 20-30 r / min, continuing stirring for 5 minutes, and heating the mixture to 65-75° C. to obtain an aqueous phase;

[0048] Step 2: Mix the oil-based auxiliary materials at 70-80°C and keep warm for 25-45 minutes to obtain the oil phase;

[0049] Step 3: mixing the antimicrobial peptide, the Artemisia annua extract and the medicinal phytomycetes extract in a mixer to obtain the main drug;

[0050] Step 4: Filter the oil phase and vacuum-absorb it into the emulsification tank, mix it with the water phase at 28-35r / min, homogenize it once at 70-80℃ at 2300-2800r / min for 4-7min through a homogenizer, add the main drug and homogenize it for the second time, and control it at 5-10℃ and 2300-2800r / min for 2-4min in a cold water bath.

[0051] Furthermore, the preparation method of modified gelatin includes: adding a surfactant sodium alkyl sulfate and deionized water, stirring and heating to 50°C, and after complete dissolution, adjusting the reaction pH to 8.0-9.0, adding gelatin, continuing to stir until the gelatin is completely dissolved, adding monoepoxy-terminated polysiloxane, reacting for 24 hours until the primary amine content no longer changes, stopping stirring and heating, and obtaining a modified gelatin solution.

[0052] Further, the preparation method of modified gelatin includes, by weight: 0.1-0.5 parts of sodium alkyl sulfate, 90-105 parts of deionized water, 3-6g of gelatin, and the amount of monoepoxy-terminated polysiloxane is 0.8 times the molar amount of primary amino groups in the gelatin molecule;

[0053] Furthermore, the preparation method of Artemisia annua extract includes weighing a crushed sample, soaking the plant dry powder with 5 times the amount of ethanol, and standing at room temperature for 12 hours; ultrasonic extraction for 2 hours; vacuum filtration, continuous extraction for 3 times, combining the filtrate, concentrating it with a rotary evaporator at 45°C, drying it, and storing it at 4°C for future use.

[0054] Furthermore, the preparation method of the medicinal pore fungus extract includes: crushing the medicinal pore fungus fruiting body and passing it through a 40-80 mesh sieve to obtain the medicinal pore fungus fruiting body powder, weighing the medicinal pore fungus fruiting body powder, adding 5 times the amount of 1,3-butanediol aqueous solution to the medicinal pore fungus fruiting body powder, stirring and extracting at a temperature of 60-70°C for 2-3h, filtering and collecting the filtrate, concentrating it with a rotary evaporator at 45°C, drying it, and storing it at 4°C for standby use.

[0055] Furthermore, a homogenizing device is used, and the homogenizing device is preferred. The homogenizing device includes a homogenizing device body 1, a rotation control motor 2, a connecting shaft 3 and a homogenizing auxiliary mechanism; a rotation control motor 2 is arranged on the homogenizing device body 1, one end of the rotation control motor 2 is connected to the connecting shaft 3, the connecting shaft 3 extends into the inner cavity of the homogenizing device body 1, and the connecting shaft 3 is connected to the homogenizing auxiliary mechanism.

[0056] The features and performance of the present invention are further described in detail below in conjunction with the embodiments.

[0057] For this embodiment,

[0058] Step 1: firstly mix water, disodium ethylenediaminetetraacetic acid and ethylparaben, add modified gelatin solution and carbomer under stirring, overnight, filter, add sorbitol and triethanolamine to the filtrate under stirring rate of 20-30r / min, continue stirring for 5 minutes, and heat to 65-75°C to obtain a water phase;

[0059] Step 2: Mix the oil-based auxiliary materials at 70-80°C and keep warm for 25-45 minutes to obtain the oil phase;

[0060] Step 3: mixing the antimicrobial peptide, the Artemisia annua extract and the medicinal phytomycetes extract in a mixer to obtain the main drug;

[0061] Step 4: Filter the oil phase and vacuum-absorb it into the emulsification tank, mix it with the water phase at 28-35r / min, homogenize it at 70-80℃ at 2300-2800r / min for 4-7min, add the main drug and homogenize it for the second time, control it at 5-10℃ and 2300-2800r / min for 2-4min in a cold water bath.

[0062] The embodiments and comparative examples were tested at the same level according to the following method, wherein:

[0063] (1) The standard of product stability test is: the prepared cream is milky yellow, and the cream droplet size is less than 9 μm under microscopic observation, and is evenly dispersed in the cream matrix. There is no stratification or demulsification after centrifugation at 3000 rpm for 30 minutes;

[0064] (2) Stability test: Pour the same amount of the drug composition to be tested evenly into a culture dish and observe it at rest;

[0065] (2) Hot and cold cycle stability test

[0066] Test conditions: The samples of each group were sealed with oxygen barrier and placed in the fresh-keeping room of the refrigerator. After 48 hours, they were taken out and placed in a 40℃ oven for 48 hours. The cycle was repeated three times. After the test, the same parameters were used to conduct the hot and cold cycle test and observe the particle size under a microscope.

[0067] Take out and place in a constant temperature box at 30℃ for long-term storage, and observe the particle size under a microscope;

[0068] In order to more intuitively demonstrate the stability, thermal stability and antioxidant process advantages of the present invention, the present invention and the same process using an equivalent replacement method are compared.

[0069] Comparative Example 1:

[0070] The preparation method is the same as that of the example, except that: in the preparation process of this comparative example, the antimicrobial peptide is replaced by tachyplesin Ⅲ with tachyplesin Ⅰ;

[0071] Comparative Example 2:

[0072] The preparation method is the same as that of the embodiment, except that: in the preparation process of this comparative example, no modified gelatin solution is added;

[0073] Comparative Example 3:

[0074] The preparation method is the same as that of the embodiment, except that: in the preparation process of this comparative example, a gelatin solution of the same content and concentration purchased from the market is added;

[0075] Comparative Example 4:

[0076] The preparation method is the same as that of the embodiment, except that: in the preparation process of this comparative example, low temperature one-time homogenization is adopted, and a gelatin solution of the same content and concentration purchased from the market is added;

[0077] And the determination was carried out according to the following method: The specific results are as follows:

[0078] Table 1: Experimental comparison of stability of modified gelatin and antimicrobial peptides in pharmaceutical compositions

[0079]

[0080]

[0081] According to the data analysis in Table 1:

[0082] (1) The results of the products tested in Example 1 and Comparative Example 1 show that the antimicrobial peptide is tachyplesin III antimicrobial peptide compared to other types of tachyplesin I; the anti-inflammatory composition containing tachyplesin III antimicrobial peptide has better dual properties of resistance to cold and high temperature, can meet the needs of high and low temperature secondary homogenization, and the antimicrobial peptide after homogenization has higher activity and no agglomeration phenomenon, such as Figure 1 and Figure 2 ; The formation of agglomeration may be caused by the fact that the antimicrobial peptide tachyplesin Ⅰ is not resistant to high temperature.

[0083] (2) The results of the products tested in the examples and comparative examples 1-4 show that the anti-inflammatory composition containing antimicrobial peptides prepared in the examples of the present invention is stable in nature and has no crystal aggregation and agglomeration phenomenon.

[0084] Among them, the products tested in the embodiment and comparative examples 1-3 are relatively stable in the short-term stability of 48h, and will not produce the problem of stratification. This may be due to the use of high and low temperature secondary homogenization to prepare, which satisfies the problem of insufficient dispersibility after adding antimicrobial peptides, Artemisia annua extract and medicinal porphyra extract. High and low temperature secondary homogenization has better stability in the short term than low temperature primary homogenization.

[0085] Comparative Example 4 uses low-temperature one-time homogenization and does not use modified gelatin solution, which will also produce certain stratification in the 48h short-term stability and does not meet the standard requirements of the product stability test.

[0086] This may be because this product is prepared by high and low temperature secondary homogenization of drug extracts, aqueous phase, oil phase and emulsifier, which meets the problem of insufficient dispersion of antimicrobial peptides, Artemisia annua extract and medicinal pore fungus extract in the main drugs. High and low temperature secondary homogenization has better stability in the short term than low temperature primary homogenization; it is stable after long-term storage and is not easily separated from oil and water.

[0087] (3) After long-term stability test, the anti-inflammatory compositions of Comparative Examples 2 and 3 showed obvious demulsification, oil-water separation, obvious centrifugal stratification, and crystal aggregation. Figure 3 and Figure 4 After the hot and cold cycle test, the hot and cold stability of the embodiment is stable, and there is no crystal aggregation phenomenon. Figure 1 .

[0088] Among them, the comparison between the embodiment and comparative example 3 shows that although the same amount of gelatin solution is added to comparative example 3, after the hot and cold cycle test, the cream shows obvious demulsification and oil-water separation, obvious centrifugal stratification, and crystal aggregation. The state of crystal aggregation is different from the agglomeration phenomenon of high temperature denaturation of antimicrobial peptides, and has a certain granular feel. The applicant infers that it may be caused by the precipitation of complex active substances in the drug extract;

[0089] Therefore, the modified gelatin solution can have a positive effect on the thermal stability of the product. The applicant infers that the modified gelatin solution has hydrophilic groups and hydrophobic groups, which can form a stable phase containing antimicrobial peptides, Artemisia annua extract, aqueous phase, oil phase and emulsifier, and this phase will not be affected by high temperature and cause stratification; while the gelatin solution has not been modified, so it does not have the ability to form a stable phase with the drug extract, aqueous phase, oil phase and emulsifier, which leads to obvious demulsification and oil-water separation after the hot and cold cycle test, obvious centrifugal stratification, and especially the phenomenon of crystal aggregation.

[0090] In summary:

[0091] (1) The present invention creatively adds the antimicrobial peptide tachyplesin III, which has excellent dual properties of cold resistance and high temperature resistance, can meet the needs of high and low temperature secondary homogenization, and the antimicrobial peptide activity after homogenization is relatively high.

[0092] (2) The present invention creatively introduces high and low temperature secondary homogenization to solve the problem of insufficient dispersibility after adding antimicrobial peptides, Artemisia annua extract and medicinal porphyra extract to the main drug, and utilizes a homogenizing device to further solve the problem of forming a stable phase of water phase, oil phase and emulsifier, and the phase will not be separated by high and low temperature secondary homogenization, and has better stability in the short term;

[0093] (3) The invention creatively introduces a modified gelatin solution, which can have a positive effect on the thermal stability of the product. The modified gelatin solution has hydrophilic groups and hydrophobic groups, and can form a stable phase containing antimicrobial peptides, artemisia annua extract and medicinal porphyrin extract with the water phase, oil phase and emulsifier. In addition, the high and low temperature secondary homogenization can solve the problem of insufficient dispersion of the antimicrobial peptides, artemisia annua extract and medicinal porphyrin extract in the main drug and maintain long-term stability. The use of a homogenizing device can further solve the problem of forming a stable phase with the water phase, oil phase and emulsifier, and the phase will not be separated due to the high and low temperature secondary homogenization.

[0094] As a further study of the present invention, as embodiment 2 of the present invention: on the basis of embodiment 1, please refer to Figure 5-Figure 12The homogenization auxiliary mechanism includes a fixed cylinder 401, a delivery pipe 402, a control pump body 403, a rotating connector 404, a movable sleeve 405, a connecting strip 406, an immersion pipe network 407, a homogenization stirring rod 408, a first auxiliary hole 409, a connecting vertical rod 410, a second auxiliary hole 411 and an auxiliary component; one end of the fixed cylinder 401 is fixedly arranged on the top of the inner cavity of the homogenization device body 1, and the other end of the fixed cylinder 401 is provided with a rotating connector 404, one side of the fixed cylinder 401 is connected with the delivery pipe 402, the delivery pipe 402 is connected to the control pump body 403, and the control pump body 403 is arranged on the homogenization device body 1, the other end of the rotating connector 404 is connected to one end of the movable sleeve 405, and the inner side wall of the bottom end of the movable sleeve 405 is equidistantly fixed with connecting strips 406, and the connecting strips 406 are fixedly arranged on the inner side wall of the bottom end of the movable sleeve 405. The other end is fixedly connected to the side wall of the connecting shaft 3, an immersion pipe network 407 is provided on the movable sleeve 405, a homogenizing stirring rod 408 is equidistantly fixedly arranged on the side wall of the movable sleeve 405, and a first auxiliary hole 409 is equidistantly arranged on the homogenizing stirring rod 408, the other end of the homogenizing stirring rod 408 is arranged on the connecting vertical rod 410, and a second auxiliary hole 411 is equidistantly arranged on the connecting vertical rod 410, and an auxiliary component is arranged on the inner side wall of the movable sleeve 405; the homogenizing stirring rod 408 is hollow, and the homogenizing stirring rod 408 is connected to the movable sleeve 405; the connecting vertical rod 410 is hollow, and is hollow and connected to the homogenizing stirring rod 408, and the homogenizing stirring rod 408 is perpendicular to the connecting vertical rod 410; the auxiliary component includes a cut-off ring 501 and a drainage auxiliary slope 502.

[0095] In this embodiment, when the material is homogenized, the oil and water floating on the top layer are guided and mixed, and enter through the immersion pipe network 407 on the movable sleeve 405, and then guided downward through the movable sleeve 405, so as to enter the interior of the material faster and better. In this process, the intercepting ring body 501 is fixedly arranged on the inner wall of the movable sleeve 405 at equal intervals, and the upper end face of the intercepting ring body 501 is arranged as a drainage auxiliary slope 502; the drainage auxiliary slope 502 is arranged in an annular shape, and the drainage auxiliary slope 502 corresponds to the pipe opening setting position of the homogenizing stirring rod 408; the inner diameter of the intercepting ring body 501 gradually decreases from top to bottom. Small; the oil and water flowing onto the intercepting ring body 501 will enter the corresponding homogenizing stirring rod 408 and the connecting vertical rod 410 from the drainage auxiliary slope 502, and then enter the material through the first auxiliary hole 409 and the second auxiliary hole 411, which can achieve better diffusion and homogenous mixing; here, a delivery pipe 402 is arranged on the delivery pipe 402, and the delivery pipe 402 here can convey the corresponding clean gas to assist the material in guiding the flow according to actual work needs, thereby improving its homogenous mixing work efficiency; and when the material causes blockage to the first auxiliary hole 409 and the second auxiliary hole 411, it has a certain auxiliary effect on eliminating the blockage of the material.

Claims

1. A method for preparing an anti-inflammatory composition containing an antimicrobial peptide, characterized in that: The preparation of the anti-inflammatory composition containing antimicrobial peptides comprises: Step 1: firstly mix water, disodium ethylenediaminetetraacetic acid and ethylparaben, add modified gelatin solution and carbomer under stirring, overnight, filter, add sorbitol and triethanolamine to the filtrate under stirring rate of 20-30r / min, continue stirring for 5 minutes, and heat to 65-75°C to obtain a water phase; Step 2: Mix the oil-based auxiliary materials at 70-80°C and keep warm for 25-45 minutes to obtain the oil phase; Step 3: Mix the antimicrobial peptide, Artemisia annua extract and medicinal phytomycetes extract in a mixer to obtain the main drug; the antimicrobial peptide is tachyplesin III, Step 4: Filter the oil phase and then decompress it into the emulsification tank, mix it with the water phase at 28-35r / min, homogenize it once at 70-80°C at 2300-2800r / min for 4-7min through a homogenizer, add the main drug and homogenize it for the second time, and control it at 5-10°C and 2300-2800r / min for 2-4min in a cold water bath. The preparation method of the modified gelatin comprises: adding a surfactant sodium alkyl sulfate and deionized water, stirring and heating to 50° C., adjusting the reaction pH to 8.0-9.0 after the gelatin is completely dissolved, adding gelatin, continuing to stir until the gelatin is completely dissolved, adding monoepoxy-terminated polysiloxane, reacting for 24 hours until the primary amine content no longer changes, stopping stirring and heating, and obtaining a modified gelatin solution.

2. The method for preparing an anti-inflammatory composition containing an antimicrobial peptide according to claim 1, characterized in that: The anti-inflammatory composition containing antimicrobial peptides comprises, by weight: 0.001-0.06 parts of antimicrobial peptides, 0.01-0.5 parts of Artemisia annua extract, 0.01-0.5 parts of medicinal porphyra extract, 15-17 parts of water-based excipients, 15-18 parts of oil-based excipients, 30-60 parts of modified gelatin solution, 0.6-1 parts of carbomer, and 136-140 parts of water. The water-based auxiliary materials are composed of disodium ethylenediaminetetraacetate, ethylparaben, sorbitol and triethanolamine in a weight ratio of (0.01-0.02): (0.01-0.02): (10-15): (1.0-2.0); The oil-based auxiliary material includes glyceryl stearate, polyethylene glycol stearate, peregal, octadecyl alcohol, and hexadecanol, wherein the weight ratio is (6-8): (1-3): (1.5-3): (1.5-3): (1.5-3).

3. The method for preparing an anti-inflammatory composition containing an antimicrobial peptide according to claim 1, characterized in that: The preparation method of the modified gelatin comprises, by weight, 0.1-0.5 parts of sodium alkyl sulfate, 90-105 parts of deionized water, 3-6g of gelatin, and the amount of monoepoxy-terminated polysiloxane used is 0.8 times the molar amount of primary amino groups in the gelatin molecule.

Citation Information

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