CN104163758B - The stearic salt derivative of 9,10,12-trihydroxy- - Google Patents

The stearic salt derivative of 9,10,12-trihydroxy- Download PDF

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Publication number
CN104163758B
CN104163758B CN201410284281.8A CN201410284281A CN104163758B CN 104163758 B CN104163758 B CN 104163758B CN 201410284281 A CN201410284281 A CN 201410284281A CN 104163758 B CN104163758 B CN 104163758B
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poly
hydroxy
trihydroxy
subtilis
preparation
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CN104163758A (en
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黄永学
刘宇
覃建华
刘练
郭鹏
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SICHUAN JINGHUA BIOTECHNOLOGY Co Ltd
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SICHUAN JINGHUA BIOTECHNOLOGY Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/01—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
    • C07C59/10—Polyhydroxy carboxylic acids
    • C07C59/105—Polyhydroxy carboxylic acids having five or more carbon atoms, e.g. aldonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/41—Preparation of salts of carboxylic acids
    • C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides compound shown in formula I, wherein, X is selected from alkali metal.Salt derivative provided by the invention, has certain anti-microbial activity, and to the anti-microbial effect of some bacterium close to antibiotic activities such as paraxin, for clinical application or daily necessities antibiotic antiseptic provide new selection.

Description

The stearic salt derivative of 9,10,12-trihydroxy-
Technical field
The present invention relates to the stearic salt derivative of 9,10,12-trihydroxy-.
Background technology
By the main path that synthetic or natural product extracting directly are household chemicals sanitas, sterilant source, but all there is certain defect in both modes, synthetic household chemicals sanitas, sterilant, as Imidurea, parabens, often its manufacturing cost is higher, and cause comparatively serious environmental pollution in manufacturing processed, the wasting of resources etc.And the material directly extracted from natural product as household chemicals sanitas, sterilant usually to have stability not good enough, water-soluble bad, the defects such as antisepsis and sterilization effect is not ideal enough.
Ricinolic acid is found to be mainly used in tensio-active agent, softening agent, lubricating oil additive etc. at present by the natural phant organic acid that perviousness is best through skin now research that retrofit obtains by Viscotrol C.Yet there are no research report ricinolic acid and derivative thereof being used for the efficient fine chemical product aspect such as sanitas, sterilant.
Summary of the invention
The object of the present invention is to provide the stearic salt derivative of 9,10,12-trihydroxy-.Another object of the present invention is to preparation method and purposes that this analog derivative is provided.
Particularly, the invention provides compound shown in formula I:
X is selected from alkali metal.
Further, X is selected from K or Na.
Present invention also offers the preparation method of above-mentioned sylvite or sodium salt compound, it comprises following operation steps:
Getting sodium hydroxide or potassium hydroxide, 9,10,12-trihydroxy-stearic acids, take ethanol as solvent, and reacting by heating is to reaction solution in neutral, and stopped reaction, removing ethanol, drying, to obtain final product.
Further, temperature of reaction is 80 ± 5 DEG C.
Further, sodium hydroxide or potassium hydroxide and the stearic mol ratio of 9,10,12-trihydroxy-are 1:1.
Present invention also offers above-claimed cpd and prepare the purposes in anti-bacterial drug.
Further, described bacterium is subtilis, streptococcus aureus, Pseudomonas aeruginosa or intestinal bacteria.
Salt derivative provided by the invention, has certain anti-microbial activity, and to the anti-microbial effect of some bacterium close to antibiotic activities such as paraxin, for clinical application or daily necessities antibiotic antiseptic provide new selection.
In some embodiments, one or more compounds of the present invention can combine with one another use.Also compound of the present invention can be selected to be combined, for the preparation of the makeup that the medicine or quality guaranteed period with antibiotic effect are longer with other active agent any.
Obviously, according to foregoing of the present invention, according to ordinary technical knowledge and the means of this area, not departing under the present invention's above-mentioned basic fundamental thought prerequisite, the amendment of other various ways, replacement or change can also be made.
Below by way of the form of specific embodiment, foregoing of the present invention is described in further detail again.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following embodiment.All technology realized based on foregoing of the present invention all belong to scope of the present invention.
Accompanying drawing explanation
Fig. 1 subtilis is 48h growth curve in different concns poly-hydroxy sodium ricinoleate
The growth curve of Fig. 2 subtilis in different concns poly-hydroxy potassium ricinoleate
Embodiment
The preparation of embodiment 1 derivative of the present invention
The ethanolic soln of the sodium hydroxide (potassium) of equivalent is added drop-wise to poly-hydroxy ricinolic acid in the solution of ethanol at 80 DEG C, after being added dropwise to complete, reaction mixture continues to stir 1-1.5h and is as cold as room temperature until the PH of reaction solution is 7. reaction solutions, decompression removing ethanol, the faint yellow solid obtained is sodium (potassium) salt of poly-hydroxy ricinolic acid after drying, yield >98%. fusing point: 202-208 DEG C (sylvite is consistent with the fusing point of sodium salt).
1HNMR (400MHz) (DMSO-d 6) 0.85 (t, 3H), 1.23-1.38 (m, 24H), 1.85 (t, 2H), 3.17-3.59 (m, 3H), 4.6 (br, 3H) (sylvite).
1HNMR (400MHz) (DMSO-d 6) 0.81 (t, 3H), 1.17-1.42 (m, 24H), 1.79 (t, 2H), 3.10-3.60 (m, 3H), 4.6 (br, 3H) (sodium salt).
Beneficial effect of the present invention is illustrated below by way of test example.
Test example 1 anti-microbial activity is tested
According to anti-microbial activity test ordinary method and poly-hydroxy ricinate (sylvite prepared by embodiment 1 or sodium salt, below can be called poly-hydroxy potassium ricinoleate or poly-hydroxy sodium ricinoleate) have characteristic, select water as solvent carrier, test the inhibition of poly-hydroxy ricinolic acid salt pair Gram-negative bacteria, gram-positive microorganism respectively.
(1) anti-microbial activity test adopts the measuring method of Odontothrips loti minimal inhibitory concentration:
According to anti-microbial activity testing method configuration different concns gradient: 100,50,25,12.5,6.25,3.13,1.56 (mg/ml) sample solution, and select the representative mushroom of Gram-negative bacteria, gram-positive microorganism: subtilis, streptococcus aureus, Pseudomonas aeruginosa, intestinal bacteria, carry out the anti-microbial activity test experiments of system.
Wherein the test data of poly-hydroxy sodium ricinoleate is as follows:
Table 1
Wherein the test data of poly-hydroxy potassium ricinoleate is as follows:
Table 2
Note: in table 1,2, "+" representative has obvious anti-microbial activity, and "+" is more, and activity is stronger; It is not obvious that "-" represents anti-microbial activity, and the diameter of inhibition zone in the digitized representation sterilization experiment in form, numerical value is larger, and bacteriostatic activity is stronger.
From table 1,2, poly-hydroxy sodium ricinoleate to subtilis, streptococcus aureus, Pseudomonas aeruginosa, colibacillary minimal inhibitory concentration is respectively: 1.56,3.13,6.25,50 (mg/ml); Poly-hydroxy potassium ricinoleate subtilis, streptococcus aureus, Pseudomonas aeruginosa, colibacillary minimal inhibitory concentration is respectively: 1.56,6.25,12.5,50 (mg/ml).
(2) growth curve method measures
Sample concentration is on each impact for examination bacteria growing state and minimal inhibitory concentration thereof:
A, subtilis 48h growth curve in different concns poly-hydroxy sodium ricinoleate the results are shown in Figure 1
B, the growth curve of subtilis in different concns poly-hydroxy potassium ricinoleate: the results are shown in Figure 2
Result shows: intuitively can reflect that different concns sample is on the impact of thalli growth state and minimal inhibitory concentration thereof by growth curve of bacteria, along with the increase of sample concentration, curve is tending towards straight line, suppress obviously to thalli growth, as above figure can find out that poly-hydroxy sodium ricinoleate and poly-hydroxy potassium ricinoleate are 1.56mg/ml to subtilis minimal inhibitory concentration, consistent with Odontothrips loti result.
(3) poly-hydroxy sodium ricinoleate and poly-hydroxy potassium ricinoleate are relative to the titration of antibiotics Chloramphenicol
With subtilis and Pseudomonas aeruginosa for representing bacterial classification, test sample controls paraxin gradient concentration germ resistance.
Preparation chloromycetin solution concentration is 200,150,100,75,50,37.5,25,18.75,12.5,9.38,6.25,4.69 (mg/ml), and the subtilis of activation 24h, Pseudomonas aeruginosa are diluted to 10 7individual/ml.Get 2ml respectively to add to lower than in 50 DEG C of LB substratum, every dull and stereotyped 20ml, makes the flat board that carries disease germs, equidistant placement Oxford cup, and the sample 200ul that annotates, each bacterium three parallel controls, repeats for three times.
Table 3
Mean diameter:
Table 4
Concentration 200 150 100 75 50 37.5 25 18.75 12.5 9.38 6.25 4.69
Log concentration 2.30 2.18 2 1.88 1.70 1.57 1.40 1.27 1.1 0.97 0.8 0.67
Ko subtilis bar 1.31 1.23 1.15 1.07 0.99 0.93 0.86 0.8 0.8 0.8 0.8 0.8
P. aeruginosa 2.0 1.86 1.66 1.46 1.26 1.15 0.98 0.91 0.88 0.86 0.83 0.8
Chloramphenicol concentration logarithmic value and Bacillus subtillis antibacterial circle diameter typical curve: regression equation: y=0.4907x+1.656, R 2=0.9964
Chloramphenicol concentration logarithmic value and Pseudomonas aeruginosa antibacterial circle diameter typical curve: regression equation: y=1.1569x-0.6710, R 2=0.9949
If the poly-hydroxy sodium ricinoleate got when concentration is 100mg/ml and poly-hydroxy potassium ricinoleate are to the antibacterial circle diameter of subtilis and Pseudomonas aeruginosa, can be calculated it and be equivalent to tiring of antibiotics Chloramphenicol and be respectively:
Table 5
Result shows: tiring of water-soluble sample poly-hydroxy sodium ricinoleate salt pair subtilis when concentration is 100mg/ml and Pseudomonas aeruginosa, be equivalent to paraxin 5.02,111.94 (mg/ml) respectively, sample poly-hydroxy potassium ricinoleate is tired to subtilis and Pseudomonas aeruginosa, be equivalent to paraxin 1.69 respectively, 61.66 (mg/ml)
Conclusion: comprehensive above-mentioned test is known, salt derivative prepared by the present invention possesses certain anti-microbial activity, wherein, poly-hydroxy sodium ricinoleate is to subtilis, streptococcus aureus, Pseudomonas aeruginosa, colibacillary minimal inhibitory concentration is respectively: 1.56,3.13,6.25,50 (mg/ml); Poly-hydroxy potassium ricinoleate is to subtilis, streptococcus aureus, Pseudomonas aeruginosa, colibacillary minimal inhibitory concentration is respectively: 1.56,6.25,12.5,50 (mg/ml), further, to the anti-microbial activity of some bacterium close to paraxin.
Test example 2 derivative of the present invention is on the impact of daily necessities
The skin care product formula of design containing poly-hydroxy ricinate, calculate the using dosage of poly-hydroxy ricinate according to formulation Design Principle, exemplify formula as follows: squalane 200 parts, white oil 400 parts, stearyl alcohol 100 parts, glyceryl monostearate 50 parts, deionized water 900 parts, glycerine 200 parts, polyoxyethylene glycol (200 gather) 200 parts, poly-hydroxy ricinate 40 parts.
Prepare containing poly-hydroxy ricinate cold cream frost finished product: 1, by formula in deionized water, glycerine, polyoxyethylene glycol, poly-hydroxy ricinate mixing, be heated with stirring to 80 DEG C for subsequent use; 2, squalane, white oil, stearyl alcohol, glyceryl monostearate etc. are heated with stirring to are molten into transparent oily liquid completely, about 72 DEG C; 3, slowly added to by the aqueous phase in 1 step in the whirlpool of 2 step oil phases, aqueous phase adds complete, and stirring velocity is modulated 1000r/min, emulsification 20min; 4, system temperature is down to 45 DEG C, adds appropriate amount of essence and skin-care effect composition; 5, continue system temperature to be down to normal temperature, bottling, the cold cream frost finished product by the time containing poly-hydroxy ricinolic acid salt component.Do not add the cold cream frost finished product of poly-hydroxy ricinate in contrast with the preparation of identical composition and engineering condition simultaneously.
The frost finished product of the cold cream containing poly-hydroxy ricinolic acid salt component produced and reference product are placed in normal temperature physical environment and store more than 3 months, add poly-hydroxy ricinate finished product (experimental group) to occur without denaturalization phenomenon, cold cream frost finished product (control group) not adding poly-hydroxy ricinate then have go mouldy, the generation of the phenomenon such as denseness reduction.
Result shows that poly-hydroxy ricinate has good antisepsis and sterilization and emulsifying property.Although salt derivative anti-microbial activity prepared by the present invention can not surmount microbiotic, its anti-microbial activity can have excellent application prospect completely to make it in the Antimicrobial preservative of household chemicals.

Claims (7)

1. compound shown in formula I:
X is selected from alkali metal, and described alkali metal does not comprise Na.
2. compound according to claim 1, is characterized in that: X is selected from K.
3. the preparation method of compound described in claim 2, is characterized in that: it comprises following operation steps:
Getting potassium hydroxide, 9,10,12-trihydroxy-stearic acids, take ethanol as solvent, and reacting by heating is to reaction solution in neutral, and stopped reaction, removing ethanol, drying, to obtain final product.
4. preparation method according to claim 3, is characterized in that: temperature of reaction is 80 ± 5 DEG C.
5. preparation method according to claim 3, is characterized in that: potassium hydroxide and the stearic mol ratio of 9,10,12-trihydroxy-are 1:1.
6. compound described in claim 1 or 2 is preparing the purposes in anti-bacterial drug.
7. purposes according to claim 6, is characterized in that: described bacterium is subtilis, streptococcus aureus, Pseudomonas aeruginosa or intestinal bacteria.
CN201410284281.8A 2014-06-23 2014-06-23 The stearic salt derivative of 9,10,12-trihydroxy- Active CN104163758B (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02215743A (en) * 1989-02-15 1990-08-28 Sannopuko Kk Production of aqueous dispersion of carboxylic acid salt
CN101618369A (en) * 2009-07-24 2010-01-06 东北大学 Hematite low temperature flotation agent and preparation method thereof
CN102504820A (en) * 2011-09-28 2012-06-20 厦门大学 Preparation method of up-conversion fluorescence/paramagnetic difunctional nanocrystal

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH02215743A (en) * 1989-02-15 1990-08-28 Sannopuko Kk Production of aqueous dispersion of carboxylic acid salt
CN101618369A (en) * 2009-07-24 2010-01-06 东北大学 Hematite low temperature flotation agent and preparation method thereof
CN102504820A (en) * 2011-09-28 2012-06-20 厦门大学 Preparation method of up-conversion fluorescence/paramagnetic difunctional nanocrystal

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
20731-56-0;Registry;《STN ON The WEB》;19841116;3 *

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Denomination of invention: L-lactic dehydrogenase 10 as one new kind of polypeptide and polynucleotides encoding this polypeptide

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