CN110368484B - Icaritin-tyrosineistocide composition suspension for inhibiting staphylococcus aureus - Google Patents
Icaritin-tyrosineistocide composition suspension for inhibiting staphylococcus aureus Download PDFInfo
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- CN110368484B CN110368484B CN201910588268.4A CN201910588268A CN110368484B CN 110368484 B CN110368484 B CN 110368484B CN 201910588268 A CN201910588268 A CN 201910588268A CN 110368484 B CN110368484 B CN 110368484B
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- icaritin
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- staphylococcus aureus
- ester composition
- stabilizer
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Abstract
The invention relates to a composition suspension for inhibiting staphylococcus aureus, in particular to an icaritin-tyrosineisthenil composition suspension for inhibiting staphylococcus aureus, which comprises 1) an icaritin-tyrosineisthenil composition, which comprises 1 of icaritin-tyrosineisthenil and a sedum lineare isopropanol extract in a weight ratio of 1; 2) A stabilizer comprising a primary stabilizer and a secondary stabilizer in a weight ratio of 22 to 30; and 30 water; wherein the structural formula of the icaritin-tyrosingopeptide ester is shown as the formula (1) and/or the formula (2);
Description
Technical Field
The invention relates to a composition suspension for inhibiting staphylococcus aureus, in particular to an icaritin-tyrosinehrlin ester composition suspension for inhibiting staphylococcus aureus and application thereof.
Background
Staphylococcus aureus, also known as Staphylococcus aureus, has a cell wall containing 90% peptidoglycan and 10% teichoic acid. The reticular structure of peptidoglycan is more compact than that of gram-negative bacteria, crystal violet is not decolorized by alcohol and is purple when dyeing, and on the contrary, the cell wall peptidoglycan layer of the negative bacteria is thin, the crosslinking degree is poor, the lipid content is high, so that the purple compound is washed away by alcohol and then is attached with sallow red. Staphylococcus aureus has been found to be a great source with penicillin. In the current year, fleming was found to kill some of the bacteria found in his culture dish of Staphylococcus aureus, and penicillin was found. The study also shows that penicillin only has obvious effect on gram-positive bacteria represented by staphylococcus aureus. This is also caused by the thickness and structure of the peptidoglycan layer. Can decompose glucose, maltose, lactose and sucrose, and produce acid and no gas. The methyl red reaction is positive, and the VP reaction is weak and positive. Many strains break down arginine, hydrolyze urea, reduce nitrate, and liquefy gelatin. The staphylococcus aureus has strong resistance, is sensitive to antibiotics such as sulfonamides, penicillin, erythromycin, terramycin, neomycin and the like, but is easy to generate drug resistance because the strains generate penicillinase and the like.
Staphylococcus aureus can be inhibited by various existing antibiotics (such as vancomycin and the like) in a planktonic state, but once a remarkable bacterial biofilm is formed, the staphylococcus aureus has extremely high drug resistance and higher clinical mortality. In the process of forming a biofilm of staphylococcus aureus, the change and regulation of extracellular proteins and virulence factors are important factors influencing the formation of the biofilm, and are also main reasons for the toxicity of the staphylococcus aureus to a host. At present, medicines capable of regulating and controlling the biofilm formation of staphylococcus aureus are very lacking.
The above background disclosure is only for the purpose of assisting understanding of the inventive concept and technical solutions of the present invention, and does not necessarily belong to the prior art of the present patent application, and should not be used for evaluating the novelty and inventive step of the present application in the case that there is no clear evidence that the above content is disclosed at the filing date of the present patent application.
Disclosure of Invention
The invention aims to provide the icaritin-tyrosinopeptide ester composition suspension for inhibiting staphylococcus aureus and the application thereof, wherein the composition in the suspension has proper particle size, uniform distribution and good stability, the injection irritation is greatly reduced, the individual administration adaptability is obviously enhanced, the suspension is not easy to generate particle aggregation and sedimentation, the storage time and the storage stability of the suspension are prolonged, and the effect of inhibiting staphylococcus aureus is favorably exerted by the suspension.
The technical scheme adopted by the invention for realizing the purpose is as follows:
[1] an icaritin-tyrosineistocide composition suspension comprises
-an icaritin-tyrosingopeptide ester composition comprising icaritin-tyrosingopeptide ester and a sedum lineare isopropanol extract in a weight ratio of 1;
-a stabilizer comprising a primary stabilizer and a secondary stabilizer in a weight ratio of 22 to 30; and
-water;
wherein the structural formula of the icaritin-tyrosingopeptide ester is shown as a formula (1) and/or a formula (2);
in the summary and preferred embodiment of the present invention, the step of preparing the icaritin-tyrosingopeptide ester comprises:
a mixing step: under the ice-water bath, 0.1mmol of icaritin and 50mg of anhydrous potassium carbonate are added into 5mL of dry acetone and stirred for 10min;
a reaction step: adding 80-100 mg of tyrosins bright peptide into the mixed solution in the mixing step, stirring for reaction in an ice water bath, and stirring for reaction at room temperature;
a purification step: the reaction solution was filtered, and the filtrate was evaporated to dryness and then subjected to silica gel column chromatography (petroleum ether: acetone = 5.
In the step of preparing the icaritin-tyrosingopeptide ester, the method for adding the tyrosingopeptide is to dissolve the tyrosingopeptide in 1-5 mL of dry acetone and then slowly drop the tyrosingopeptide in an amount of 10-20 min/mL.
In the step of preparing the icaritin-tyrosingopeptide ester, the reaction time is 2-4 h under the condition of stirring in ice-water bath.
In the step of preparing the icaritin-tyrosingopeptide ester, the reaction time is 12 to 24 hours under stirring at room temperature.
The icaritin-tyrosinamine acid ester prepared by the method has higher yield of final products, higher proportion of 3,5 and 7, higher proportion of esterification products, is more favorable for improving the biological utilization rate of the icaritin-tyrosinamine acid ester and enhancing the inhibition effect of the icaritin-tyrosinamine acid ester on staphylococcus aureus, can play a more efficient role in inhibiting the staphylococcus aureus after being compatible with a sedum lineare isopropanol extract, and can obviously inhibit the formation of staphylococcus aureus biomembranes, reduce the drug resistance of the icaritin-tyrosine acid ester composition suspension, and effectively inhibit or even kill bacteria on free staphylococcus aureus.
In the summary and the preferred embodiment of the invention, the linear stonecrop herb isopropanol extract is prepared by leaching the whole linear stonecrop herb with ethanol solution, sequentially extracting the leaching solution with petroleum ether, ethyl acetate and isopropanol, taking the isopropanol extract, and drying to obtain the linear stonecrop herb isopropanol extract.
The ethanol solution is 50-85% of ethanol water solution by volume fraction.
The leaching temperature is 35-55 ℃.
The leaching time is 30 min-4 h.
In the summary and the preferred embodiment of the present invention, the weight ratio of the icaritin-tyrosingopeptide ester composition to the stabilizer is 1.
The main stabilizer is at least one selected from cetyl trimethyl quaternary ammonium salt, tween 20, span 80, serum protein, sodium dodecyl sulfate, sugar and polyalcohol.
The secondary stabilizer is amino acid and cholic acid derivatives with the weight ratio of 1.
The sugar and the polyol in the primary stabilizer are selected from at least one of glycerin, mannitol, and sorbitol.
The amino acid in the secondary stabilizer is at least one selected from glycine, arginine, aspartic acid and glutamine.
The cholic acid derivative in the secondary stabilizer is at least one selected from lithocholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, sodium taurocholate and tauroursodeoxycholic acid.
In particular, the "primary" and "secondary" of the primary and secondary stabilizers are not only for ease of distinction and reference to different stabilizers, but also differ in their amounts and roles. For example, but not limited to, the stabilizer comprises a primary stabilizer and a secondary stabilizer in a weight ratio of 25 to 1, the primary stabilizer is sodium dodecyl sulfate, and the secondary stabilizer is glycine and deoxycholic acid in a weight ratio of 1 to 4; for example, but not limited to, the weight ratio of primary stabilizer to secondary stabilizer in the stabilizer is 28; the stabilizer may also include, for example but not limited to, a primary stabilizer and a secondary stabilizer in a weight ratio of 26 to 1, wherein the primary stabilizer is cetyl trimethyl quaternary ammonium salt and glycerin in a weight ratio of 1 to 5, and the secondary stabilizer is glutamine and tauroursodeoxycholic acid in a weight ratio of 1 to 3.5. According to the method, the primary stabilizer and the secondary stabilizer with different performances and contents are matched, and the primary stabilizer and the secondary stabilizer are cooperatively matched to improve the stability of the medicine particle icaritin-tyrosine ester composition in suspension, so that the suspension is not easy to generate the defects of particle aggregation and sedimentation in the storage process, the storage time and the storage stability of the composition suspension are prolonged, the composition in the obtained icaritin-tyrosine ester composition suspension is proper in particle size, uniform in distribution and good in stability, compared with an oil solution, the irritation of intramuscular injection is greatly reduced, the individual administration adaptability is remarkably enhanced, a certain slow release effect is achieved, and the bioavailability is further improved.
In the present invention, the icaritin-tyrosinopeptide ester composition comprising icaritin-tyrosinopeptide ester and a phorodiazole isopropyl alcohol extract is an effective active ingredient in the suspension preparation of the present invention, and in one embodiment of the present invention, the icaritin-tyropeptide ester composition preparation is a suspension of the icaritin-tyropeptide ester composition, wherein the content of the icaritin-tyropeptide ester composition is 2 to 60% (g/mL), preferably 5 to 40% (g/mL), more preferably 15 to 30% (g/mL), for example, but not limited to, 2 to 60% (g/mL), 5 to 60% (g/mL), 10 to 60% (g/mL), 20 to 60% (g/mL), 30 to 60% (g/mL), 40 to 60% (g/mL), 50 to 60% (g/mL), 2 to 50% (g/mL), 5 to 50% (g/mL), 10 to 50% (g/mL), 20 to 50% (g/mL), 30 to 50% (g/mL), 40 to 40% (g/mL), 2 to 40% (g/mL), or 40 to 40% (g/mL), 2 to 40% (g/mL), or the like, 5-30% (g/mL), 10-30% (g/mL), 20-30% (g/mL), 2-20% (g/mL), 5-20% (g/mL), 10-20% (g/mL), 2-100% (g/mL), 5-10% (g/mL), 2-5% (g/mL) and any definite value within the range; for example, but not limited to, the following specific amounts may be used: 2% (g/mL), 5% (g/mL), 7% (g/mL), 10% (g/mL), 12% (g/mL), 15% (g/mL), 16% (g/mL), 17% (g/mL), 18% (g/mL), 19% (g/mL), 20% (g/mL), 21% (g/mL), 22% (g/mL), 23% (g/mL), 24% (g/mL), 25% (g/mL), 26% (g/mL), 27% (g/mL), 28% (g/mL), 29% (g/mL), 30% (g/mL), 31% (g/mL), 32% (g/mL), 33% (g/mL), 34% (g/mL), 35% (g/mL), 40% (g/mL), 45% (g/mL), 50% (g/mL), 55% (g/mL), 60% (g/mL) and any of two content numerical ranges.
Without being bound by theory, if the concentration of the effective active ingredients is higher than the upper limit of 60% (g/mL), more active ingredients are released at the early stage, which may exceed the effective treatment concentration and bring about the waste of activity; if the concentration of the active ingredient is less than 2% (g/mL), the release amount is small and the effective therapeutic concentration cannot be achieved, and the slow release cannot be maintained and the drug effect cannot be exerted for a long period of time. The icaritin-tyrosinopeptide ester composition in the icaritin-tyrosinopeptide ester composition suspension has the advantages of proper particle size, uniform distribution and good stability, compared with an oil solution, the irritation of intramuscular injection is greatly reduced, the individual administration adaptability is obviously enhanced, a certain slow release effect is realized, and the bioavailability is further improved; the icaritin-tyrosinopeptide ester and the sedum lineare isopropanol extract are compatible to play a role in efficiently inhibiting staphylococcus aureus, the icaritin-tyropeptide ester composition suspension can obviously inhibit the formation of staphylococcus aureus biofilms, reduces the drug resistance of the staphylococcus aureus biofilms, effectively inhibits or even kills bacteria of free staphylococcus aureus, integrally and efficiently inhibits a staphylococcus aureus rescue ball quorum sensing system, effectively reduces the return of the staphylococcus aureus rescue ball quorum sensing system to the drug-resistant biofilm phenotype, and provides high-value reference for the preparation of specific preparations for inhibiting the formation of the staphylococcus aureus biofilms in medicine.
In one embodiment of the present invention, in the suspension of the icaritin-tyrosineester composition, the weight ratio of the icaritin-tyrosineester composition to the stabilizer is 1.5 to 40, preferably 1 to 30, more preferably 1 to 20, and for example, but not limited to the following range ratio: 1.5 to 40, 1 to 25, 1 to 35, 1; for example but not limited to 2: 12. 1, 1.
In one embodiment of the present invention, the icaritin-tyrosingopeptide ester composition suspension comprises at least one of the following items (1) to (8):
(1) The content of the icaritin-tyrosingopeptide ester composition is 15-30% (g/mL);
(2) In the icaritin-tyroselintide ester composition, the weight ratio of the icaritin-tyroselintide ester to the linear stonecrop herb isopropanol extract is 1;
(3) The weight ratio of the primary stabilizer to the secondary stabilizer in the stabilizer is 22-30;
(4) The main stabilizer is at least one selected from cetyl trimethyl quaternary ammonium salt, tween 20, span 80, serum protein, sodium dodecyl sulfate, sugar and polyalcohol;
(5) The sugar and polyol are selected from at least one of glycerol, mannitol, and sorbitol;
(6) The secondary stabilizer is amino acid and cholic acid derivatives with the weight ratio of 1;
(7) The amino acid is at least one selected from glycine, arginine, aspartic acid and glutamine;
(8) The cholic acid derivative is selected from at least one of lithocholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, sodium taurocholate and tauroursodeoxycholic acid.
In one embodiment of the invention, the icaritin-tyrosingopeptide ester composition suspension comprises the following components:
preferably, the icaritin-tyrosingopeptide ester composition suspension comprises the following components:
the icaritin-tyrosingopeptide ester composition suspension can be directly applied to a human body, for example, through intramuscular injection. Before the icaritin-tyrosineistocide composition suspension is used, shaking is needed to be carried out to improve the uniform stability of the suspension. Without being limited by theory, the suspension for intramuscular injection can be agglomerated at the injection part after injection to form a drug storage, the dissolved drug enters the systemic circulation to achieve the effect of slow release and can play a role in efficiently inhibiting staphylococcus aureus, the icaritin-tyrosineistocide composition suspension can obviously inhibit the formation of staphylococcus aureus biofilms, reduce the drug resistance of the staphylococcus aureus biofilms, effectively inhibit and even kill bacteria on free staphylococcus aureus, and integrally and efficiently inhibit a staphylococcus aureus rescue ball group induction system.
[2] The method for preparing any one of the icaritin-tyrosinehelipside composition suspensions described in item [1] of the present invention specifically comprises the following steps:
a mixing step, namely uniformly mixing the primary stabilizer, the secondary stabilizer and water to obtain a first mixed solution;
a re-dissolving step, namely adding the icaritin-tyramine kefir ester and the veronicastrum herb isopropanol extract into the mixed solution and uniformly mixing to obtain a second mixed solution;
a high-speed homogenizing step, in which the second mixed solution is homogenized at a high speed to obtain a third mixed solution;
a high-pressure homogenizing step, which is to homogenize the third mixed solution under high pressure to obtain the product.
In one embodiment of the present invention, the high pressure homogenization step comprises:
-150 to 300bar for at least 5 cycles; preferably 5 to 10 cycles, such as 8 to 10 cycles, for example 10 cycles;
5 to 10 cycles, for example 5 to 8 cycles, for example 8 cycles, at 700 to 1000 bar;
5 to 10 cycles, for example 6 to 8 cycles, for example 8 cycles, at 400 to 600 bar;
5 to 10 cycles, for example 7 to 9 cycles, for example 9 cycles, at 1100 to 1300 bar.
In one embodiment of the invention, preferably, 150-300 bar cycles until there is no appreciable impact sound of the ceramic bead with the valve seat.
[3] An icaritin-tyrosineLeucin ester composition freeze-dried preparation, which is prepared by freeze-drying any one of icaritin-tyrosineLeucin ester composition suspension described in item [1] or item [2] of the invention.
In one embodiment of the present invention, the lyoprotectant is selected from at least one of dextran, glycerol, mannitol, inositol, raffinose, and trehalose;
in one embodiment of the invention, the lyoprotectant is used in an amount of 5 to 50 wt.%, preferably 10 to 40 wt.%, more preferably 15 to 35 wt.% of the solid content.
[4] The use of the icaritin-tyrosinopeptide ester composition suspension of any item [1] or [2] and/or the icaritin-tyropeptide ester composition freeze-dried preparation of any item [3] in the preparation of preparations for inhibiting staphylococcus aureus, wherein the uses include but are not limited to:
-use in the manufacture of a medicament for inhibiting staphylococcus aureus; and/or
-use in the preparation of a staphylococcus aureus vaccine formulation; and/or
-use in the manufacture of a medicament for inhibiting biofilm formation in staphylococcus aureus; and/or
-use in the manufacture of a medicament for reducing the pathogenicity of a virulence factor of staphylococcus aureus; and/or
Application in the preparation of medicines for inhibiting the quorum sensing system of the grape rescue ball.
The icaritin-tyrosineLeucin ester composition suspension or the icaritin-tyrosineLeucin ester composition freeze-dried preparation has the effect of effectively inhibiting staphylococcus aureus, can obviously reduce the pathogenicity of staphylococcus aureus, obviously inhibit the formation of staphylococcus aureus biomembranes, reduce the drug resistance of the staphylococcus aureus composition suspension or the icariteLeucin ester composition freeze-dried preparation, effectively inhibit or even kill bacteria of free staphylococcus aureus, and integrally inhibit a staphylococcus aureus rescue capsule quorum sensing system with high efficiency, so that the icariteLeucin-tyrosineLeucin ester composition suspension or the icariteLeucin-tyrosineLeucin ester composition freeze-dried preparation can be applied to the fields of medicines for inhibiting staphylococcus aureus, staphylococcus aureus vaccines, staphylococcus aureus biofilm formation inhibition, staphylococcus aureus virulence factor pathogenicity reduction, staphylococcus aureus rescue capsule sensing systems and the like.
The invention has the beneficial effects that:
1) According to the method, the primary stabilizer and the secondary stabilizer with different performances and contents are matched, and the primary stabilizer and the secondary stabilizer are cooperatively matched to improve the stability of the medicine particle icaritin-tyrosine ester composition in suspension, so that the suspension is not easy to generate the defects of particle aggregation and sedimentation in the storage process, the storage time and the storage stability of the composition suspension are prolonged, the composition in the obtained icaritin-tyrosine ester composition suspension has proper particle size, uniform distribution and good stability, compared with an oil solution, the irritation of intramuscular injection is greatly reduced, the individual administration adaptability is remarkably enhanced, a certain slow release effect is realized, and the bioavailability is further improved;
2) The icaritin-tyramine acid ester and the linear stonecrop isopropyl alcohol extract are compatible to play a role in efficiently inhibiting staphylococcus aureus, the icaritin-tyramine acid ester composition suspension can obviously inhibit the formation of staphylococcus aureus biomembranes, reduces the drug resistance of the staphylococcus aureus biomembrane, effectively inhibits or even kills bacteria of free staphylococcus aureus, integrally inhibits a staphylococcus aureus rescue capsule quorum sensing system efficiently, effectively reduces the return of the staphylococcus aureus rescue capsule quorum to the drug-resistant biomembrane phenotype, and provides a high-value reference for preparing a specific preparation for inhibiting the formation of the staphylococcus aureus biomembrane medically;
3) The icaritin-tyrosinamine ester composition suspension is injected intramuscularly, and can be agglomerated at the injection part after injection to form a drug reservoir, and the dissolved drug enters systemic circulation to achieve the effect of slow release, thereby playing the role of efficiently inhibiting staphylococcus aureus;
4) The icaritin-tyrosineLeucin ester composition suspension or the icaritin-tyrosineLeucin ester composition freeze-dried preparation has the effect of effectively inhibiting staphylococcus aureus, can obviously reduce the pathogenicity of staphylococcus aureus, obviously inhibit the formation of staphylococcus aureus biomembranes, reduce the drug resistance of the staphylococcus aureus composition suspension or the icariteLeucin ester composition freeze-dried preparation, effectively inhibit or even kill bacteria of free staphylococcus aureus, and integrally inhibit a staphylococcus aureus rescue capsule quorum sensing system with high efficiency, so that the icariteLeucin-tyrosineLeucin ester composition suspension or the icariteLeucin-tyrosineLeucin ester composition freeze-dried preparation can be applied to the fields of medicines for inhibiting staphylococcus aureus, staphylococcus aureus vaccines, staphylococcus aureus biofilm formation inhibition, staphylococcus aureus virulence factor pathogenicity reduction, staphylococcus aureus rescue capsule sensing systems and the like.
The technical scheme is adopted to provide the model essay, so that the defects of the prior art are overcome, the design is reasonable, and the operation is convenient.
Drawings
In order to make the aforementioned and other objects, features, and advantages of the invention, as well as others which will become apparent, reference is made to the following description taken in conjunction with the accompanying drawings in which:
FIG. 1 is a schematic diagram showing the autolysis curve of the icaritin-tyrosinerebrotide ester composition suspension of the present invention against Staphylococcus aureus.
Detailed Description
Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The present invention uses the methods and materials described herein; other suitable methods and materials known in the art may be used. The materials, methods, and examples described herein are illustrative only and are not intended to be limiting. All publications, patent applications, patents, provisional applications, database entries, and other references mentioned herein, and the like, are incorporated by reference herein in their entirety. In case of conflict, the present specification, including definitions, will control.
Other features and advantages of the invention will be apparent from the following detailed description, the accompanying drawings, and the claims.
For the words "for example" and "such as" and grammatical equivalents thereof, the phrase "without limitation" should be understood to follow general usage unless explicitly stated otherwise. As used herein, the word "about" refers to variations due to experimental error. Unless expressly stated otherwise, all measurements described herein, whether or not explicitly used, are to be understood as being modified by the word "about". As used herein, the singular forms "a," "an," and "the" ("a," "an," and "the") include plural referents unless the context clearly dictates otherwise.
In one embodiment of the present invention, the icaritin-tyrosingopeptide ester is prepared in the following manner:
mixing: under the ice-water bath, 0.1mmol of icaritin and 50mg of anhydrous potassium carbonate are added into 5mL of dry acetone and stirred for 10min;
reaction: dissolving 85mg of tyrosins-leucin in 2mL of dry acetone, slowly dripping the solution into the mixed solution in the mixing step in an amount of 20min/mL, stirring and reacting for 3 hours in an ice-water bath, and stirring and reacting for 12 hours at room temperature;
and (3) purification: the reaction solution was filtered, and the filtrate was evaporated to dryness and then subjected to silica gel column chromatography (petroleum ether: acetone =5: 1) and dried to obtain 125.6mg of icaritin-tyrosinehmitin ester solid.
In one embodiment of the present invention, the icaritin-tyrosingopeptide ester is prepared in the following manner:
mixing: under the ice-water bath, 0.1mmol of icaritin and 50mg of anhydrous potassium carbonate are added into 5mL of dry acetone and stirred for 10min;
reaction: dissolving 90mg of tyrosinte in 3mL of dry acetone, slowly dripping the solution into the mixed solution in the mixing step in an amount of 20min/mL, stirring and reacting for 4 hours in an ice water bath, and stirring and reacting for 16 hours at room temperature;
and (3) purification: the reaction solution was filtered, and the filtrate was evaporated to dryness and then separated by silica gel column chromatography (petroleum ether: acetone = 5).
In one embodiment of the present invention, the icaritin-tyrosingopeptide ester is prepared in the following manner:
mixing: under the ice-water bath, 0.1mmol of icaritin and 50mg of anhydrous potassium carbonate are added into 5mL of dry acetone and stirred for 10min;
reaction: dissolving 95mg of tyrosinte in 2mL of dry acetone, slowly dripping the solution into the mixed solution in the mixing step in an amount of 15min/mL, stirring and reacting for 4 hours in an ice water bath, and stirring and reacting for 18 hours at room temperature;
and (3) purification: the reaction solution was filtered, and the filtrate was evaporated to dryness and then separated by silica gel column chromatography (petroleum ether: acetone = 5).
Example 1:
a suspension of icaritin-tyrosinopeptide ester composition comprises icaritin-tyropeptide ester composition, stabilizer and water, wherein
The weight ratio of the icaritin-tyrosingopeptide ester composition to the stabilizer is 1;
the icaritin-tyrosingopeptide ester composition comprises:
icaritin-tyrosinehelipside, and
sedum lineare isopropanol extract;
the weight ratio of the icaritin-tyrosinte to the linear stonecrop herb isopropanol extract is 1.
The preparation method of the icaritin-tyrosingopeptide ester comprises the following steps:
a mixing step: under the ice-water bath, 0.1mmol of icaritin and 50mg of anhydrous potassium carbonate are added into 5mL of dry acetone and stirred for 10min;
a reaction step: adding 80mg of tyrosins bright peptide into the mixed solution in the mixing step, stirring the mixture for reaction in an ice water bath, and stirring the mixture for reaction at room temperature;
a purification step: the reaction solution was filtered, and the filtrate was evaporated to dryness and then subjected to silica gel column chromatography (petroleum ether: acetone = 5.
In the step of preparing the icaritin-tyroselin ester, the method for adding the tyroselin ester is to dissolve the tyroselin ester in 2mL of dry acetone and then slowly drop the tyroselin ester in an amount of 15 min/mL.
In the step of preparing the icaritin-tyrosingopeptide ester, the reaction time is 2 hours under the stirring of an ice water bath.
In the step of preparing the icaritin-tyrosingopeptide ester, the reaction time is 12h under stirring at room temperature.
The icaritin-tyrosinamine acid ester prepared by the method has higher yield of final products, the ratio of the 3,5,7 position esterification products is higher, the improvement of the biological utilization rate of the icaritin-tyrosinamine acid ester is more facilitated, the inhibition effect of the icaritin-tyrosinamine acid ester on staphylococcus aureus is enhanced, the effect of inhibiting the staphylococcus aureus with higher efficiency can be exerted after the icaritin-tyrosinamine acid ester is compatible with a linear stonecrop isopropyl alcohol extract, the formation of staphylococcus aureus biomembranes can be obviously inhibited by the icaritin-tyrosinamine acid ester composition suspension, the drug resistance of the staphylococcus aureus biomembrane is reduced, and the free staphylococcus aureus can be effectively inhibited and even killed.
The stonecrop isopropyl alcohol extract is prepared by leaching the whole stonecrop herb with 75 percent ethanol solution by volume fraction at 40 ℃ for 1h, sequentially extracting the leaching solution with petroleum ether, ethyl acetate and isopropyl alcohol, taking the isopropyl alcohol extract, and drying the isopropyl alcohol extract.
The stabilizer comprises a primary stabilizer and a secondary stabilizer, wherein
The weight ratio of the primary stabilizer to the secondary stabilizer is 24;
the main stabilizer is serum protein and glycerol in a mass ratio of 1;
the secondary stabilizer is arginine and deoxycholic acid in a weight ratio of 1.
In particular, "primary" and "secondary" in the primary and secondary stabilizers are not merely for convenience of distinction and reference to different stabilizers, but also differ in their content and function. According to the method, the primary stabilizer and the secondary stabilizer with different performances and contents are matched, and the primary stabilizer and the secondary stabilizer are cooperatively matched to improve the stability of the medicine particle icaritin-tyrosine ester composition in suspension, so that the suspension is not easy to generate the defects of particle aggregation and sedimentation in the storage process, the storage time and the storage stability of the composition suspension are prolonged, the composition in the obtained icaritin-tyrosine ester composition suspension is proper in particle size, uniform in distribution and good in stability, compared with an oil solution, the irritation of intramuscular injection is greatly reduced, the individual administration adaptability is remarkably enhanced, a certain slow release effect is achieved, and the bioavailability is further improved.
In the present invention, the icaritin-tyrosineLeucin ester composition consisting of icaritin-tyrosineLeucin ester and phorodi isopropyl alcohol extract is an effective active ingredient in the suspension formulation of the present invention, and in one embodiment of the present invention, the icaritin-tyrosineLeucin ester composition formulation, when it is an icaritin-tyrosineLeucin ester composition suspension, wherein the content of the icaritin-tyrosineLeucin ester composition is 16% (g/mL).
The icaritin-tyrosinopeptide ester composition in the icaritin-tyrosinopeptide ester composition suspension has the advantages of proper particle size, uniform distribution and good stability, compared with an oil solution, the irritation of intramuscular injection is greatly reduced, the individual administration adaptability is obviously enhanced, a certain slow release effect is realized, and the bioavailability is further improved; the icaritin-tyrosinopeptide ester and the sedum lineare isopropanol extract are compatible to play a role in efficiently inhibiting staphylococcus aureus, the icaritin-tyropeptide ester composition suspension can obviously inhibit the formation of staphylococcus aureus biofilms, reduces the drug resistance of the staphylococcus aureus biofilms, effectively inhibits or even kills bacteria of free staphylococcus aureus, integrally and efficiently inhibits a staphylococcus aureus rescue ball quorum sensing system, effectively reduces the return of the staphylococcus aureus rescue ball quorum sensing system to the drug-resistant biofilm phenotype, and provides high-value reference for the preparation of specific preparations for inhibiting the formation of the staphylococcus aureus biofilms in medicine.
In an embodiment, the icaritin-tyrosingopeptide ester composition suspension comprises the following features (1) to (5):
(1) The content of the icaritin-tyrosingopeptide ester composition is 16% (g/mL);
(2) In the icaritin-tyrosinte composition, the weight ratio of the icaritin-tyrosinate to the sedum lineare isopropanol extract is 1;
(3) The weight ratio of the primary stabilizer to the secondary stabilizer in the stabilizer is 24;
(4) The main stabilizer is serum protein and glycerol in a mass ratio of 1;
(5) The secondary stabilizer is arginine and deoxycholic acid in a weight ratio of 1.
In this embodiment, the icaritin-tyrosingopeptide ester composition suspension comprises the following components:
the icaritin-tyrosingopeptide ester composition suspension can be directly applied to a human body, for example, through intramuscular injection. Before the icaritin-tyrosineistocide composition suspension is used, shaking is needed to be carried out to improve the uniform stability of the suspension. Without being limited by theory, the suspension for intramuscular injection can be agglomerated at the injection part after injection to form a drug storage, the dissolved drug enters the systemic circulation to achieve the effect of slow release and can play a role in efficiently inhibiting staphylococcus aureus, the icaritin-tyrosineismin ester composition suspension can significantly inhibit the formation of staphylococcus aureus biofilms, reduce the drug resistance of the staphylococcus aureus biofilms, effectively inhibit or even kill bacteria of free staphylococcus aureus, and integrally and efficiently inhibit a staphylococcus aureus rescue ball colony induction system.
The method for preparing the icaritin-tyrosingopeptide ester composition suspension in the embodiment specifically comprises the following steps:
a mixing step, namely uniformly mixing the primary stabilizer, the secondary stabilizer and water to obtain a first mixed solution;
a re-dissolving step, adding icaritin-tyrosinte and the isopropanol extract of sedum lineare into the mixed solution and mixing evenly to obtain a second mixed solution;
a high-speed homogenizing step, in which the second mixed solution is homogenized at a high speed to obtain a third mixed solution;
a high-pressure homogenizing step, which is to homogenize the third mixed solution under high pressure to obtain the product.
In one embodiment of the present invention, the high pressure homogenization step comprises:
10 cycles at 200 bar;
900bar under 8 cycles;
8 cycles at 500 bar;
1250bar for 9 cycles.
In one aspect, the invention relates to the use of any one of the icaritin-tyrosineLeutide ester composition suspension and/or icaritin-tyrosineLeutide ester composition freeze-dried preparation in the preparation of a preparation for inhibiting staphylococcus aureus, wherein the uses include but are not limited to:
-use in the manufacture of a medicament for inhibiting staphylococcus aureus; and/or
-use in the preparation of a staphylococcus aureus vaccine formulation; and/or
-use in the manufacture of a medicament for inhibiting biofilm formation in staphylococcus aureus; and/or
-use in the manufacture of a medicament for reducing the pathogenicity of a virulence factor of staphylococcus aureus; and/or
-use in the manufacture of a medicament for inhibiting the quorum sensing system of a rescuee of Vitis vinifera.
The icaritin-tyrosinopeptide ester composition suspension or the icaritin-tyrosinopeptide ester composition freeze-dried preparation has the effect of effectively inhibiting staphylococcus aureus, can obviously reduce the pathogenicity of staphylococcus aureus, obviously inhibit the formation of staphylococcus aureus biofilms, reduce the drug resistance of staphylococcus aureus, effectively inhibit or even kill bacteria of free staphylococcus aureus, and integrally and effectively inhibit a staphylococcus aureus rescue sphere quorum sensing system, so that the icaritin-tyropeptide ester composition suspension or the icaritin-tyropeptide ester composition freeze-dried preparation can be applied to the fields of medicines for inhibiting staphylococcus aureus, staphylococcus aureus vaccines, staphylococcus aureus biofilm formation inhibition, low staphylococcus aureus virulence factor pathogenicity, staphylococcus aureus rescue sphere quorum sensing system inhibition and the like.
Example 2:
example 2 provides a suspension of an icaritin-tyrosinehrlin ester composition, and example 2 is substantially the same as example 1 except that: the primary stabilizer in example 2 consisted of 30.72g of sodium dodecyl sulfate and 30.72g of mannitol; the secondary stabilizer consisted of 0.512g aspartic acid and 2.048g chenodeoxycholic acid.
Example 3:
example 3 provides a suspension of an icaritin-tyrosinehriin ester composition, and example 3 is substantially the same as example 1 except that: the primary stabilizer in example 3 was 61.44g serum protein; the secondary stabilizer consists of 0.512g of glutamine and 2.048g of sodium taurocholate.
Comparative example V4:
comparative example V4 provides a suspension of an icaritin-tyrosingopeptide ester composition, and comparative example V4 is substantially the same as example 1 except that: comparative example V4 contained no secondary stabilizer and the amount of the shortage was 100mL supplemented with water.
Comparative example V5:
comparative example V5 a suspension of an icaritin-tyrosinehmitin ester composition is provided, comparative example V5 being substantially the same as example 1 except that: comparative example V5 contained no main stabilizer, and the amount of shortage was 100mL supplemented with water.
Comparative example V6:
comparative example V6 provides a suspension of an icaritin-tyrosingopeptide ester composition, and comparative example V6 is substantially the same as example 1 except that: the secondary stabilizer of comparative example V6 is 2.56g arginine.
Comparative example V7:
comparative example V7 provides a suspension of an icaritin-tyrosingopeptide ester composition, and comparative example V7 is substantially the same as example 1 except that: the secondary stabilizer of comparative example V7 was 2.56g of deoxycholic acid.
Example 8:
Experimental example 1:
and (3) particle size distribution measurement:
the particle size distribution of the icaritin-tyrosineRaphide ester composition suspensions of examples 1 to 3 and comparative examples V4 to V7 and the freeze-dried preparation of the icaritin-tyrosineRaphide ester composition of example 8 were measured, which specifically included the following:
A. laboratory sample and instrument
Icaritin-tyrosinopeptide ester composition suspensions of examples 1 to 3 and comparative examples V4 to V7;
the icaritin-tyrosinehriin ester composition lyophilized formulation of example 8;
malvern 2000 laser granulometer.
B. Experimental methods
Cleaning and adjusting a laser particle size analyzer, adding suspension into pure water, enabling the light shading rate to reach 10-20%, and then measuring the particle size;
the lyophilized preparation was diluted 100-fold with pure water, dispersed by sonication, and then the particle size was measured.
C. Results of the experiment
As shown in table 1 below. As can be seen from Table 1, the particle size distribution of the icaritin-tyrosineLeucin ester composition suspensions in the preferred embodiments 1 to 3 of the present invention is relatively uniform, the particle size at 10% of the cumulative particle size distribution is 0.21 to 0.25 μm, the particle size at 50% of the cumulative particle size distribution is 1.05 to 1.15 μm, and the particle size at 90% of the cumulative particle size distribution is 2.50 to 2.75 μm, and the particle size of the suspension (the suspension in embodiment 1) is only slightly increased when the suspension is prepared into the lyophilized preparation (embodiment 8), which means that the particle size distribution of the suspension prepared into the lyophilized preparation of the icaritin-tyrosineLeucin ester composition of the present invention is not greatly affected. The influence of the change of the stabilizer in the system on the particle size is larger, specifically, the particle size of the suspension is greatly increased when only the main stabilizer is used alone or only the secondary stabilizer is used alone, the D50 is more than 2.6 μm, and the D90 is more than 4.0 μm; and when the secondary stabilizer only contains amino acid or cholic acid derivatives, the particle size of the suspension is also changed sharply, wherein D50 is more than 2.6 mu m, and D90 is more than 4.0 mu m, which shows that the primary stabilizer and the secondary stabilizer with special proportion can bring proper particle size and uniform particle size distribution to the icaritin-tyrosine leucin ester composition suspension.
TABLE 1 results of particle size distribution
| Examples | D10(μm) | D50(μm) | D90(μm) |
| 1 | 0.215 | 1.050 | 2.545 |
| 2 | 0.215 | 1.125 | 2.740 |
| 3 | 0.248 | 1.085 | 2.562 |
| V4 | 0.240 | 2.835 | 4.115 |
| V5 | 0.652 | 2.656 | 4.025 |
| V6 | 0.285 | 2.568 | 3.852 |
| V7 | 0.268 | 2.552 | 3.722 |
| 8 | 0.256 | 1.205 | 2.990 |
Experimental example 2:
particle size stability measurement 1:
the method of experimental example 1 was repeated to measure the particle size of the suspension after the icaritin-tyrosineismic acid ester composition suspension prepared in example 1 was allowed to stand at room temperature for 0d, 20d, 40d, 60d, 80d, 100d, 120d and 140d, so as to measure the storage stability of the icaritin-tyrosineismic acid ester composition suspension of the present invention, and the results of the measurement of particle size are shown in table 2. As can be seen from Table 2, after long-term storage, the particle size of the icaritin-tyrosinehriin ester composition suspension did not increase greatly, no agglomeration occurred, indicating that the storage stability was excellent.
Table 2, results of suspension storage stability (particle size) in example 1
| Storage time | D10(μm) | D50(μm) | D90(μm) |
| 0d | 0.215 | 1.050 | 2.545 |
| 20d | 0.218 | 1.052 | 2.545 |
| 40d | 0.226 | 1.054 | 2.546 |
| 60d | 0.234 | 1.059 | 2.548 |
| 80d | 0.248 | 1.062 | 2.550 |
| 100d | 0.260 | 1.066 | 2.553 |
| 120d | 0.282 | 1.071 | 2.559 |
| 140d | 0.305 | 1.075 | 2.560 |
Particle size stability determination 2:
the method of experimental example 1 was repeated to measure the particle size of the icaritin-tyrosineLeucin ester composition suspension prepared in example 3 and comparative examples V5-V6 after standing at room temperature for 0d, 5d, 10d, 15d, and 20d, so as to measure the storage stability of the icaritin-tyrosineLeucin ester composition suspension, and the results of measuring the particle size are shown in Table 3. As can be seen from Table 3, after long-term storage, the icaritin-tyrosinehensin ester composition suspension of example 3 has excellent particle size stability and small particle size change, and compared with the comparative examples 5 and 6, the particle size change is large, the suspension has obvious agglomeration and agglomeration phenomena, and the stability is poor, so that the composition is not suitable for popularization and application.
Table 3, example 3 and comparative examples V5 to V6 results of the storage stability (particle size) of the suspension
Example 9:
example 9 provides a suspension of the composition, and example 9 is essentially the same as example 1, except that: the suspension in example 9 comprises the following components: 16.0g of icaritin-tyrosineprotein ester, 30.72g of serum protein, 30.72g of glycerol, 0.512g of arginine, 2.048g of deoxycholic acid and 100mL of water.
Example 10:
example 10 provides a suspension of the composition, and example 10 is essentially the same as example 1, except that: the suspension in example 10 comprises the following components: 16.0g of sedum lineare isopropanol extract, 30.72g of serum protein, 30.72g of glycerol, 0.512g of arginine, 2.048g of deoxycholic acid and 100mL of water.
Example 11:
example 11 provides a suspension of the composition, and example 11 is essentially the same as example 1, except that: the suspension in example 11 comprises the following components: 0.01g of icaritin-tyrosinehrline, 15.99g of sedum lineare isopropanol extract, 30.72g of serum protein, 30.72g of glycerol, 0.512g of arginine, 2.048g of deoxycholic acid and 100mL of water.
Example 12:
example 12 provides a suspension of the composition, and example 12 is essentially the same as example 1, except that: the suspension in example 12 comprises the following components: 15.99g of icaritin-tyrosinehrline, 0.01g of isopropanol extract of sedum lineare, 30.72g of serum protein, 30.72g of glycerol, 0.512g of arginine, 2.048g of deoxycholic acid and 100mL of water.
Example 13:
example 13 provides a suspension of the composition, and example 13 is essentially the same as example 1, except that: the suspension in example 13 comprises the following components: 30.72g of serum protein, 30.72g of glycerol, 0.512g of arginine, 2.048g of deoxycholic acid and 100mL of water.
Experimental example 3:
determination of Minimum Inhibitory Concentration (MIC):
the drug resistance inhibition effect was studied using human-derived staphylococcus aureus (a strain sample obtained from the center for disease prevention and control) as a starting strain and vancomycin as a positive control, with each suspension obtained in example 1, example 2, comparative examples V4 to V7, and examples 9 to 13 as a study target. Selecting and culturing the pure bacterial colony for 18-24 h, uniformly dissolving the pure bacterial colony in a 2-5 mLLB liquid culture medium, adjusting the turbidity of the pure bacterial colony to be equal to that of a 0.5 McLeod turbiditube, and measuring the OD600 value of the pure bacterial colony by using an enzyme-labeling instrument. A suspension diluent with the concentration of 30mg/mL is prepared by using dimethyl sulfoxide as a liquid medicine, the liquid medicine, a bacterial liquid and an LB liquid culture medium are added into a 96-hole culture plate by using a test tube double dilution method for overnight culture, and liquid medicine groups with different concentrations are all three in parallel, so that the reliability of experimental data is ensured.
And (3) measuring the Minimum Inhibitory Concentration (MIC) of the suspension to the multidrug-resistant staphylococcus aureus by using a microplate reader. And placing the culture solution with the MIC concentration in a sterile LB liquid culture medium for continuous culture, and determining the Minimum Bactericidal Concentration (MBC) of the suspension of the invention to the drug-resistant staphylococcus aureus by using a microplate reader, wherein the measurement results are shown in Table 4. As can be seen from Table 4, the icaritin-tyrofibrutin ester composition suspensions in the preferred embodiments 1 and 2 of the invention have better inhibitory effect on drug-resistant Staphylococcus aureus, the MIC of the composition can reach 28.5 mu g/mL, and the MBC can reach 225 mu g/mL.
TABLE 4 inhibition of drug-resistant Staphylococcus aureus by the icaritin-tyrosineistocide ester composition suspension of the present invention
Function of
Experimental example 4:
determination of the effect on bacterial autolysis:
A. grouping (5 replicates per group):
taking each suspension in example 1 (E1), comparative example V7 (EV 7) and examples 9-13 (E9-E12) as an experimental group, diluting by 400 times, adding 1mL into 9mL of basic culture solution, inoculating staphylococcus aureus with the initial concentration of 7 × 107CFU/mL, and standing and culturing at 37 ℃ for 24h;
inoculating staphylococcus aureus with 10mL pure basic culture solution as a blank group (B) and allowing the initial concentration of the staphylococcus aureus to be 7 multiplied by 107CFU/mL, and standing and culturing at 37 ℃ for 24h;
staphylococcus aureus was inoculated at an initial concentration of 7X 107CFU/mL in 10mL of a basal medium containing 20. Mu.g/mL of penicillin sodium as a control group (C), and incubated at 37 ℃ for 24 hours.
B. Culturing:
centrifuging each group at 3000r/min for 10min, discarding the supernatant, and resuspending the pellet obtained from each replicate treatment with mL of PBS buffer containing 0.05% triton x-100;
C. and (3) determination:
200mL of the resuspended bacterial solution was pipetted into a microplate, the initial absorbance (initial OD value) at 595nm was measured using an microplate reader, the OD value at 595nm was measured every hour, and an autolysis curve was prepared using time as abscissa and relative OD value (ratio of OD value at each time point to initial OD value) as ordinate.
D. As a result:
referring to fig. 1, it can be seen that the autolysis curve in the preferred embodiment 1 of the present invention is close to that of the penicillin sodium group, while the relative OD values of the remaining comparative examples V7 and 9-13 are only slightly greater than that of the control group, i.e., the icaritin-tyrosinehramide composition suspension in the preferred embodiment 1 of the present invention can effectively inhibit the autolysis of staphylococcus aureus, which can result in the decrease of autolysis rate of bacteria, the failure of normal binary division of bacteria, the appearance of two, three or even four sub-cell clusters, and the bacteriostatic and bactericidal effects.
Conventional techniques in the above embodiments are known to those skilled in the art, and thus will not be described in detail herein.
The above embodiments are merely illustrative, and not restrictive, and those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention. Therefore, all equivalent technical solutions also belong to the scope of the present invention, and the protection scope of the present invention should be defined by the claims.
Claims (11)
1. An icaritin-tyrosingopeptide ester composition suspension, which is characterized by comprising:
-an icaritin-tyrosingopeptide ester composition comprising icaritin-tyrosingopeptide ester and a sedum lineare isopropanol extract in a weight ratio of 1;
-a stabilizer comprising a primary stabilizer and a secondary stabilizer in a weight ratio of 22 to 30; and
-water;
wherein the structural formula of the icaritin-tyrosingopeptide ester is shown as a formula (1) and/or a formula (2);
the sedum lineare isopropanol extract is prepared by leaching sedum lineare with ethanol solution, sequentially extracting the leaching solution with petroleum ether, ethyl acetate and isopropanol, taking isopropanol extract, and drying to obtain sedum lineare isopropanol extract; wherein the ethanol solution is ethanol water solution with the volume fraction of 50-85%; the leaching temperature is 35-55 ℃; the leaching time is 30 min-4 h;
the main stabilizer is selected from at least one of cetyl trimethyl quaternary ammonium salt, tween 20, span 80, serum protein, sodium dodecyl sulfate and polyalcohol;
the secondary stabilizer is amino acid and cholic acid derivatives with the weight ratio of 1.
2. The suspension of claim 1, wherein the step of preparing the icaritin-tyrosingopeptide ester comprises:
a mixing step: under the ice-water bath, 0.1mmol of icaritin and 50mg of anhydrous potassium carbonate are added into 5mL of dry acetone and stirred for 10min;
a reaction step: adding 80-100 mg of tyrosins bright peptide into the mixed solution in the mixing step, stirring the mixture in an ice water bath for reaction, and then stirring the mixture at room temperature for reaction;
a purification step: filtering the reaction solution, evaporating the filtrate to dryness, and separating by silica gel column chromatography with petroleum ether, acetone =5 as an eluent to obtain the product.
3. The suspension of claim 2, wherein the addition of tyroselinopeptide is performed by dissolving tyroselinopeptide in 1-5 mL of dry acetone followed by slow addition of tyroselinopeptide in an amount of 10-20 min/mL.
4. A suspension according to any of claims 1 to 3, characterized in that:
the polyol is selected from at least one of glycerol, mannitol and sorbitol;
the amino acid is at least one selected from glycine, arginine, aspartic acid and glutamine;
the cholic acid derivative is selected from at least one of lithocholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, sodium taurocholate and tauroursodeoxycholic acid.
5. A method for preparing the suspension of the icaritin-tyrosingopeptide ester composition of any one of claims 1 to 4, comprising:
a mixing step, namely uniformly mixing the primary stabilizer, the secondary stabilizer and water to obtain a first mixed solution;
a re-dissolving step, adding icaritin-tyrosinte and the isopropanol extract of sedum lineare into the mixed solution and mixing evenly to obtain a second mixed solution;
a high-speed homogenizing step, in which the second mixed solution is homogenized at a high speed to obtain a third mixed solution;
a high-pressure homogenization step, in which the third mixed solution is high-pressure homogenized to obtain the final product.
6. The method of claim 5, wherein: the high-pressure homogenizing step comprises the following steps:
-150 to 300bar for at least 5 cycles;
-700-1000 bar with 5-10 cycles;
5 to 10 cycles at-400 to 600 bar;
5 to 10 cycles at 1100 to 1300 bar.
7. A lyophilized preparation of an icaritin-tyrosingopeptide ester composition, which is prepared by lyophilizing the suspension of any one of claims 1 to 4.
8. The use of the icaritin-tyrosineLeucin ester composition suspension of any one of claims 1 to 4 or the icaritin-tyrosineLeucin ester composition lyophilized formulation of claim 7, characterized in that the use comprises:
-use in the manufacture of a medicament for inhibiting staphylococcus aureus; and/or
-use in the preparation of a staphylococcus aureus vaccine formulation.
9. The use of the icaritin-tyrosineLeucin ester composition suspension of any one of claims 1 to 4 or the lyophilized formulation of the icaritin-tyrosineLeucin ester composition of claim 7, wherein the use comprises:
-use in the manufacture of a medicament for inhibiting biofilm formation in staphylococcus aureus.
10. The use of the icaritin-tyrosineLeucin ester composition suspension of any one of claims 1 to 4 or the lyophilized formulation of the icaritin-tyrosineLeucin ester composition of claim 7, wherein the use comprises:
-use in the preparation of a medicament for reducing the pathogenicity of virulence factors of staphylococcus aureus.
11. The use of the icaritin-tyrosineLeucin ester composition suspension of any one of claims 1 to 4 or the icaritin-tyrosineLeucin ester composition lyophilized formulation of claim 7, characterized in that the use comprises:
-use in the manufacture of a medicament for inhibiting the quorum sensing system of staphylococcus aureus.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK112814B (en) * | 1966-01-16 | 1969-01-20 | Mogensen M Sode | Process for the preparation of the antibacterial active substances, whole caseicidin, α-caseicidin, β-caseicidin and γ-caseicidin. |
| WO1982003771A1 (en) * | 1981-04-30 | 1982-11-11 | Mitsuhashi Susumu | Polysaccharide ps-a isolated from the plant of genus epimedium violaceum morr,et decne.,process for its preparation,and infection-preventing agent and immunostimulating agent containing the polysaccharide as effective ingredient |
| CN101239028A (en) * | 2008-03-10 | 2008-08-13 | 中山大学 | Bathing agent using schizonepeta tenuifolia to inhibit staphylococcus aureus |
| CN109276544A (en) * | 2018-11-12 | 2019-01-29 | 中国医学科学院药用植物研究所 | A kind of hydrated icaritin nanoparticle and its preparation method and application |
-
2019
- 2019-07-02 CN CN201910588268.4A patent/CN110368484B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK112814B (en) * | 1966-01-16 | 1969-01-20 | Mogensen M Sode | Process for the preparation of the antibacterial active substances, whole caseicidin, α-caseicidin, β-caseicidin and γ-caseicidin. |
| WO1982003771A1 (en) * | 1981-04-30 | 1982-11-11 | Mitsuhashi Susumu | Polysaccharide ps-a isolated from the plant of genus epimedium violaceum morr,et decne.,process for its preparation,and infection-preventing agent and immunostimulating agent containing the polysaccharide as effective ingredient |
| CN101239028A (en) * | 2008-03-10 | 2008-08-13 | 中山大学 | Bathing agent using schizonepeta tenuifolia to inhibit staphylococcus aureus |
| CN109276544A (en) * | 2018-11-12 | 2019-01-29 | 中国医学科学院药用植物研究所 | A kind of hydrated icaritin nanoparticle and its preparation method and application |
Non-Patent Citations (4)
| Title |
|---|
| 24味中药对金黄色葡萄球菌生物膜作用的研究;崔新洁等;《时珍国医国药》;20170520(第05期);第1079-1081页 * |
| 淫羊藿不同提取物的体外抑菌实验研究;张振巍等;《中国药师》;20161205(第12期);第2247-2250页 * |
| 淫羊藿甙的提取及抑菌作用;严赞开等;《江苏农业科学》;20060730(第04期);第56-57,107页 * |
| 金黄色葡萄球菌生物膜形成机制及中药调控作用的研究进展;李新圃等;《中兽医医药杂志》;20181210(第06期);第21-25页 * |
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