CN114560963A - Preparation method and application of chitosan azelaic acid and derivatives thereof - Google Patents
Preparation method and application of chitosan azelaic acid and derivatives thereof Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
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- 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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/736—Chitin; Chitosan; Derivatives thereof
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
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Abstract
The invention discloses a preparation method and application of a chitosan azelaic acid derivative, which comprises the step 1 that chitosan and azelaic acid are subjected to carboxylation reaction in isopropanol medium under an alkaline condition to generate chitosan azelaic acid. Step 2, performing structural characterization by using an infrared spectrum, and confirming the generation of chitosan azelaic acid by using a result; step 3, comparing the bacteriostatic effect of the new synthesized chitosan derivative on the inoculum by the chitosan azelaic acid derivative and the single solutions of chitosan and azelaic acid to obtain the strong bacteriostatic effect of the new synthesized chitosan derivative; and 4, step 4: by comparing the gel prepared from chitosan azelaic acid with the recombinant human collagen functional dressing for treating facial acne, repairing laser wound, preventing early pigmentation of the wound, observing and comparing the conditions of two groups of patients, and observing the occurrence of adverse events in the treatment process, the product obtained by the method has remarkable advantages in treating acne and promoting wound healing.
Description
Technical Field
The invention relates to the field of chitosan derivatives, in particular to a preparation method and application of chitosan azelaic acid and chitosan azelaic acid derivatives.
Background
Chitosan is a deacetylated chitin product, is a natural alkaline polysaccharide, has excellent biocompatibility and biodegradability, and can be easily prepared into various derivatives. Because of its abundant source, non-toxic, and solubility in acetic acid and other organic acids, it has been widely used in industry and medicine. Especially, in the antibacterial property, in recent years, chitosan has attracted much attention as a natural antibacterial agent, but the antibacterial activity of chitosan is low compared with that of the traditional antibacterial agent, and chitosan is insoluble in water and only soluble in some dilute acid solutions, thereby limiting the application of chitosan in many aspects. At present, the existing methods for chemically modifying chitosan mainly comprise acylation modification, etherification modification, alkylation modification, esterification modification, quaternization modification, carboxylation modification, guanidine modification and the like.
The active groups on the chitosan molecule, namely hydroxyl and amino, can be used as acting groups during modification. The sugar residue of chitosan molecular chain has active hydroxyl and amino. One is a primary hydroxyl group C6-OH, the other being a secondary hydroxyl group C3-OH，C6OH activity greater than C3OH, by chemical reaction, C6OH can form a series of hydroxyl derivatives. The amino group on the chitosan belongs to a primary amino group, and H on N is more active and can generate a plurality of reactions to generate a series of N-derivatives. Therefore, these groups can be modified by introducing different groups. The modified chitosan derivative has wider application prospect in the aspects of metal adsorption, flocculating agent, medicine, enzyme carrier, cell solidification, agricultural chemical preparation and the like.
Azelaic Acid (Azelaic Acid, AZA) is also known as Azelaic Acid, a natural straight-chain saturated dicarboxylic Acid containing 9 carbon atoms and having a molecular weight of 188.22. It has the following functions: 1. the azelaic acid can inhibit the protein synthesis of bacteria, directly inhibit aerobic bacteria and anaerobic bacteria on the surface of skin and in hair follicles, and has the killing effect on staphylococcus epidermidis, pseudomonas aeruginosa, proteus, candida albicans, propionibacterium acnes and the like at higher concentration (more than 250 mmol/L). 2. For treating pigmentation, abnormal change of skin pigment cells leads to increased pigment synthesis and abnormal cell proliferation, and causes melasma, malignant freckle and other pigmentation diseases. Azelaic acid can inhibit tyrosinase activity in abnormal pigment cells and inhibit pigment synthesis; also inhibit abnormal pigment cell DNA synthesis and mitochondrial enzyme activity, reduce cell proliferation activity, and prevent malignant lentigo from developing into malignant melanoma.
Acne, also called comedo, is a chronic inflammatory skin disease that occurs in the pilosebaceous glands, well in puberty. The occurrence of acne mainly comprises 3 causes: firstly, the level of androgen testosterone in a body is too high, the androgen is converted into dihydrotestosterone through the action of 5-alpha reductase in sebaceous glands, and the dihydrotestosterone acts to cause the sebaceous gland to be hyperfunction so that grease is excessively secreted; secondly, abnormal keratinization of keratinocyte in the hair follicle is not easy to fall off, so that cuticle is thickened and keratinized substance is accumulated, the hair follicle and sebaceous gland ducts are abnormally keratinized and blocked, sebaceous gland discharge is obstructed, and finally a keratotic plug is formed. ③ the secretion and discharge of a large amount of sebum are obstructed, and bacterial infections in hair follicles, such as Propionibacterium acnes, Staphylococcus epidermidis and Malassezia are liable to occur, among which the anaerobic Propionibacterium acnes infection is most important. Azelaic acid plays a positive inhibiting and regulating role on the factors in the aspects 3, so that the function of skin cells is recovered to be normal, and the effect of treating acne is achieved.
Disclosure of Invention
Aiming at the defects in the technology, the invention provides a preparation method and application of chitosan azelaic acid, and the obtained chitosan azelaic acid is a novel bacteriostatic agent, so that the problem that the chitosan is difficult to dissolve in water is solved, the bacteriostatic effect and the application range of the chitosan are improved, and some characteristics of the azelaic acid are also reserved. Such as: bacteriostatic properties and their properties for treating acne and preventing pigmentation. And the yield almost the same as that of the traditional synthetic method is obtained in a very short time, the time is saved, and the efficiency is improved.
In order to achieve the above object, the present invention provides 1. a method for preparing chitosan azelaic acid and its derivatives, which is characterized by comprising the following steps:
s1: weighing chitosan and azelaic acid according to the requirements;
s2: adding azelaic acid into purified water for dissolving, then adding sodium hydroxide, and uniformly stirring to obtain a mixed solution of azelaic acid;
s3, dissolving chitosan in purified water, adding isopropanol, stirring uniformly, and heating in water bath to obtain chitosan mixed solution;
and S4, adding the azelaic acid mixed solution into the chitosan mixed solution, cooling after uniform mixing, then carrying out vacuum filtration, and washing with acetone to obtain chitosan azelaic acid and derivatives thereof.
Preferably, in step S1, the weight ratio of chitosan to azelaic acid is 1: (1-2).
Preferably, in step S2, sodium hydroxide is added to adjust the pH of the solution to a pH between 10 and 12.
Preferably, in step S3, the volume ratio of the isopropyl alcohol to the chitosan solution is (4-5): 1.
Preferably, in step S3, the temperature of the water bath heating is 60-80 degrees Celsius.
Preferably, in step S3, the mixture is stirred at a constant temperature after being heated in a water bath, and the stirring time at the constant temperature is 7 to 10 hours.
The invention also discloses application of the chitosan azelaic acid and the derivatives thereof, which are used for preparing cosmetics by mixing with other acceptable components.
The invention also discloses application of the chitosan azelaic acid and the derivatives thereof, which are used for preparing external medicines by mixing with other acceptable components.
The invention has the beneficial effects that: compared with the prior art, the invention provides a preparation method of the chitosan azelaic acid derivative based on the work of the prior art, the activity of chitosan amino is lower under alkaline condition, and the chitosan amino and azelaic acid are subjected to carboxylation reaction in isopropanol medium. Successful substitution of azelaic acid for C6-one H above OH, forming the chitosan azelaic acid derivative. The structure identification of the polymer is carried out through infrared spectroscopy, and the modification process of the chitosan is successfully completed. The reaction time and temperature were investigated by orthogonal experimentsThe influence of factors such as the degree, the pH value, the feed ratio of raw materials and the like on the yield determines the optimal synthesis process.
Drawings
FIG. 1 is a flow chart of the steps of the present invention;
FIG. 2 is an infrared spectrum of chitosan;
FIG. 3 is an infrared spectrum of chitosan azelaic acid;
FIG. 4 is a scanning electron micrograph of chitosan;
FIG. 5 is a scanning electron micrograph of chitosan azelaic acid.
Detailed Description
The technical solutions in the embodiments of the present application will be described clearly and completely with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are only some embodiments, not all embodiments, of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In the description of the present invention, it is to be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. indicate orientations and positional relationships based on those shown in the drawings, and are used only for convenience of description and for simplicity of description, and do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore, should not be considered as limiting the present invention. Furthermore, the terms "first" and "second" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or including indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the described features. In the description of the present invention, "a plurality" means two or more unless specifically defined otherwise.
In the present application, the word "exemplary" is used to mean "serving as an example, instance, or illustration. Any embodiment described herein as exemplary is not necessarily to be construed as preferred or advantageous over other embodiments. The following description is presented to enable any person skilled in the art to make and use the invention. In the following description, details are set forth for the purpose of explanation. It will be apparent to one of ordinary skill in the art that the present invention may be practiced without these specific details. In other instances, well-known structures and processes are not shown in detail to avoid obscuring the description of the invention with unnecessary detail. Thus, the present invention is not intended to be limited to the embodiments shown, but is to be accorded the widest scope consistent with the principles disclosed herein.
Patent No. CN200910009203.6 discloses a spot-removing skin care cosmetic containing azelaic acid, which discloses the preparation ratio of azelaic acid and chitosan, but does not disclose the specific preparation process, and the skilled in the art can not obtain chitosan azelaic acid through the patent, but the current research shows that the chitosan azelaic acid can effectively treat acne, so how to obtain chitosan azelaic acid and derivatives thereof is a problem which needs to be solved urgently at present.
Referring to fig. 1, the invention discloses a preparation method of chitosan azelaic acid and derivatives thereof, which is characterized by comprising the following steps: s1: weighing chitosan and azelaic acid according to the requirements; s2: adding azelaic acid into purified water for dissolving, then adding sodium hydroxide, and uniformly stirring to obtain a mixed solution of azelaic acid; s3, dissolving chitosan in purified water, adding isopropanol, stirring uniformly, and heating in water bath to obtain chitosan mixed solution; s4, adding the azelaic acid mixed solution into the chitosan mixed solution, cooling after uniform mixing, then carrying out vacuum filtration, and washing with acetone to obtain chitosan azelaic acid and derivatives thereof; in step S1, the mass ratio of chitosan to azelaic acid is 1: (1-2), preferably 1: 2; adding sodium hydroxide to adjust the pH value of the solution, and controlling the pH value to be between 10 and 12; in step S3, the volume ratio of the isopropanol to the chitosan dissolved solution is (4-5): 1; the temperature of water bath heating is 60-80 ℃; and (3) heating in a water bath, and stirring at constant temperature for 7-10 hours. In the implementation process, the reaction mechanism is that the hydroxyl activity of chitosan C6 in isopropanol medium under the alkaline condition of chitosan and azelaic acid is greater than that of amino, and the carboxylation reaction is carried out to generate the derivative of chitosan azelaic acid, and the reaction process is as follows:
in the actual implementation process, the whole preparation process is as follows:
1) weighing 5g of azelaic acid, adding 100ml of purified water, adding 10g of NaOH, and stirring for 2 h.
2) Weighing 10g of chitosan, putting the chitosan into a beaker, adding 150ml of purified water, then adding 750ml of isopropanol, stirring at a constant speed, and heating in a water bath to 70 ℃. Then slowly adding the product in the reaction in the step 1) and stirring for 8 hours at constant temperature.
3) And after the reactant is cooled, carrying out suction filtration on the reaction mixture by using a vacuum pump, removing the solvent, washing by using acetone, and drying to obtain the chitosan azelaic acid and the derivatives thereof.
Referring to fig. 2 and 3, the infrared spectra before and after the reaction of chitosan are substantially similar by comparing the two images; at 1477cm in FIG. 3-1Is at CH3The strong absorption peak of C-H bending vibration indicates that hydroxyl in chitosan molecule is substituted, and C is6Azelaic acid is successfully grafted on the above hydroxyl group.
Referring to fig. 4 and 5, using reactivity scanning of chitosan and chitosan azelaic acid, it can be seen that the scanning electron micrographs of chitosan show a larger regular cluster structure, which is related to a stronger force between the chitosan molecules; whereas the irregular fluffy and spherical shape shown in fig. 5 was due to the destruction of hydrogen bonds and crystalline regions within the chitosan molecule, confirming that azelaic acid has been grafted onto the chitosan molecule.
The obtained chitosan azelaic acid was subjected to a bacteriostatic test:
weighing solutions of chitosan, azelaic acid and chitosan azelaic acid with the same mass fraction, comparing the bacteriostatic effects of the inoculum according to relevant regulations of 'disinfection technical Specification' 2002 edition, and obtaining the following results:
as can be seen from the table, compared with a single component, the newly synthesized chitosan azelaic acid has the synergistic function of the two components, the antibacterial performance is greatly improved, the curative effect on pseudomonas aeruginosa, candida albicans and the like is especially improved, the solubility of chitosan is also improved, and the application range of the chitosan azelaic acid is expanded.
In the specific application process, the chitosan azelaic acid and the derivatives thereof can be applied to cosmetics or external medicines so as to achieve the effect of improving or treating acne, scars and pigmentation, but the products need to be subjected to relevant clinical tests so as to prove that the components have no toxic effect on human bodies and can be used by patients with reassurance, and in the specific application process, the chitosan azelaic acid and the derivatives thereof can be mixed with certain components, such as glycerol, glycerol stearate and the like according to the requirements.
The clinical test adopts a classic random control test design type, and the design can effectively eliminate the interference of confounding factors on test results and ensure the balance comparability of a test group and a control group. Before the test, a data statistical mechanism generates a block random scheme by using statistical software, and the grouping sequence of the testees in the test process is respectively randomly distributed and enters a test group or a control group. The control group and the test group were assigned 1:1.
The clinical trial was as follows:
and (3) experimental design: the effectiveness and the safety of the chitosan azelaic acid are evaluated by comparing the gel prepared from the chitosan azelaic acid with medical recombinant human-derived collagen functional dressing to treat facial acne, repair laser wound, prevent early pigmentation of the wound, observe and compare the difference of curative effects of two groups of patient conditions such as skin lesion healing, pigmentation, scars and other symptoms, observe the occurrence of adverse events in the treatment process and evaluate the effectiveness and the safety of the chitosan azelaic acid.
Selecting a patient: the following cases were met and the cases were included: (1) signing an informed consent and voluntarily receiving the test. (2) Age 18 to 38 years. (3) The acne diagnosis standard of Western medicine is met, the acne is diagnosed by doctors, and the acne GAGS scoring is adopted in clinical grade: mild degree is 1-18, moderate degree is 19-30, severe degree is 31-38, and skin lesion is classified as inflammatory acne.
The completion criteria are: inflammatory acne completed 7 days of treatment; treatment and observation are completed for 4 weeks after laser cosmetic surgery; and if the relevant recorder is performed, the case is finished.
The experimental procedure was as follows:
test group a: inflammatory acne is treated with a gel formulated with chitosan azelaic acid. The using method comprises the following steps: the product is taken in a proper amount and is evenly smeared on the surface of an affected part of skin twice a day.
Test group B uses a gel formulated with chitosan azelaic acid to treat pigmentation and scar repair after laser cosmetology. The using method comprises the following steps: after laser beauty treatment, a proper amount of gel prepared by the product is uniformly smeared on the surface of the skin at the treatment position for 2 times a day. The sun is avoided during the use period, and sun-proof measures are taken.
Control group a: the medical recombinant human collagen functional dressing is used for treating inflammatory acne.
The application method comprises uniformly applying appropriate amount of the composition on the affected part of skin for 2 times per day.
Control group B: the medical recombinant human collagen functional dressing is used for preventing and treating pigmentation and repairing scars after laser cosmetology. The using method comprises the following steps: after laser beauty treatment, a proper amount of medical recombinant human collagen functional dressing (gel type) is uniformly smeared on the surface of the skin of a treatment part for 2 times every day. The sun is avoided during the use period, and sun-proof measures are taken.
According to the related acne GAGS score: the good acne part is divided into 6 areas. The first area is forehead (2), the second area is right cheek (2), the third area is left cheek (2), the fourth area is nose (1), the V area is lower forehead area (1), the VI area is chest and upper back (3), and the factors of different sections are enclosed in brackets. The skin lesion score for each area is (the score for that area is determined by the skin lesion with the most severe inflammatory response in principle): 0 score: no skin, 1 score) 1 acne, 2 score) 1 papule, 3 score) 1 abscess, 4 score) 1 nodule; then the total score of the subarea is factor score multiplied by skin damage score, the sum of the total scores of different subareas is a comprehensive score, and the acne is graded into mild degree of 1-18, moderate degree of 19-30, severe degree of 31-38 and extra weight of more than 39 according to the numerical value of the comprehensive score.
The pigmentation observation indexes comprise that the two groups of patients are subjected to repeated diagnosis 1 month after the first treatment, the pigment disappears for 0 point, the pigment is faded for 1 point compared with the pigment before the treatment, the pigment is similar to the pigment before the treatment for 2 points, the pigment is slightly deepened for 3 points compared with the pigment before the treatment, and the pigment is obviously deepened for 4 points compared with the pigment before the treatment. Pigmentation rate (deepening case number + obviously deepening case number)/total case number.
3.5.3 photo taking of skin lesions: the camera is set to a medium and close range mode; the brightness is compared, and a flash lamp does not need to be started under the condition that the lamp is turned on indoors; the date is corrected and displayed; the name, age, random number and shooting date of the patient are marked on a scale; the same body position, angle and height should be noted during each shooting, the shutter is pressed after the half-press shutter is focused for 1S, and the contrast of the skin photos before and after treatment is repeated if the photos are fuzzy after shooting.
The onset time, i.e., the number of days from the first treatment when symptoms were reduced and rash had resolved by more than 30%, was recorded.
The main curative effect is as follows: skin damage therapeutic effect judgment standard
The total integral of skin damage before and after treatment is reduced by more than 90 percent;
has obvious effect, the total integral of skin damage before and after treatment is reduced by 60 to 90 percent;
the total integral of skin damage before and after treatment is reduced by 30 to 59 percent;
the total integral of skin lesions before and after treatment was reduced by < 30%.
Note: effective rate (%) - (number of cure cases + number of significant cases + number of effective cases)/total number of cases × 100% ]
The results are as follows:
the clinical test totally comprises 80 subjects, 12 laser cosmetic surgeries and 68 inflammatory acnes. The ratio of the number of the test subjects in the experimental group to the number of the test subjects in the control group is 1:1. Wherein, 40 cases are grouped into a group, 1 case of curative effect data is not removed after the missed visit, 2 cases of combined medication in violation of the scheme are removed, 3 cases are removed in total, and 37 cases are actually completed; the control group is added into 40 cases, 1 case is removed in case of violating the test scheme, 2 cases are removed in case of violating the test scheme, 3 cases are removed in total, and 37 cases are actually completed.
The demographic data of the two groups of subjects, such as age, marital, family, source, height and weight, have no statistical significance (P > 0.05), so that the demographic data of the two groups of subjects can be considered to have better comparability.
The difference of the vital signs before treatment of the two groups of subjects has no statistical significance (P is more than 0.05), and the subjects have better comparability.
The basic disease data of two groups of subjects, such as the disease course, the combined diseases, the drug allergy, the combined medication condition, the skin lesion integration before treatment, and the like, have no statistical significance (P is more than 0.05), and have better comparability.
The curative rate of the curative effect of the inflammatory acne skin lesion in the test group is 18.75 percent, and the total effective rate is 68.75 percent; the curative rate of the inflammatory acne skin lesion curative effect of the control group is 18.75 percent, and the total effective rate is 65.62 percent. The skin lesion curative effect of two groups of subjects is tested by CMH chi-square method for deducting central effect, and the difference is not statistically significant (P is more than 0.05). After the treatment course, no pigmentation occurred in both groups of subjects after laser cosmetic surgery.
The skin lesion scores of the inflammatory acnes in the two groups after the treatment course is finished are reduced compared with those before the treatment course (P is less than 0.05), the difference has statistical significance, and the differences in the two groups after the treatment course is finished have no statistical significance (P is more than 0.05).
The onset time of skin damage of an experimenter is 37.0 +/-2.38 days, the onset time of skin damage of a control group is 38.6 +/-1.88 days, and the difference between the onset time of the two groups has no statistical significance (P is more than 0.05).
The final results show that: chitosan azelaic acid and its derivatives can improve skin erythema, pimple, pustule, blackhead, acne, red blood streak, skin atrophy and thinning multiform skin lesion, and local symptoms of skin pruritus, dryness, desquamation, burning, skin tension and pain.
Having thus described the basic concept, it will be apparent to those skilled in the art that the foregoing detailed disclosure is to be considered merely illustrative and not restrictive of the broad application. Various modifications, improvements and adaptations to the present application may occur to those skilled in the art, although not explicitly described herein. Such modifications, improvements and adaptations are proposed in the present application and thus fall within the spirit and scope of the exemplary embodiments of the present application.
Also, the present application uses specific words to describe embodiments of the application. Reference throughout this specification to "one embodiment," "an embodiment," and/or "some embodiments" means that a particular feature, structure, or characteristic described in connection with at least one embodiment of the present application is included in at least one embodiment of the present application. Therefore, it is emphasized and should be appreciated that two or more references to "an embodiment" or "one embodiment" or "an alternative embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, some features, structures, or characteristics of one or more embodiments of the present application may be combined as appropriate.
Similarly, it should be noted that in the preceding description of embodiments of the application, various features are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure aiding in the understanding of one or more of the embodiments. This method of disclosure, however, is not intended to require more features than are expressly recited in the claims. Indeed, the embodiments may be characterized as having less than all of the features of a single embodiment disclosed above.
Where numerals describing the number of components, attributes or the like are used in some embodiments, it is to be understood that such numerals used in the description of the embodiments are modified in some instances by the modifier "about", "approximately" or "substantially". Unless otherwise indicated, "about", "approximately" or "substantially" indicates that the number allows a variation of ± 20%. Accordingly, in some embodiments, the numerical parameters used in the specification and claims are approximations that may vary depending upon the desired properties of the individual embodiments. In some embodiments, the numerical parameter should take into account the specified significant digits and employ a general digit preserving approach. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the range are approximations, in the specific examples, such numerical values are set forth as precisely as possible within the scope of the application.
For each patent, patent application publication, and other material cited in this application, such as articles, books, specifications, publications, documents, and the like, the entire contents of which are hereby incorporated by reference into this application, except for application history documents that are inconsistent with or conflict with the contents of this application, and except for documents that are currently or later become incorporated into this application as though fully set forth in the claims below. It is noted that the descriptions, definitions and/or use of terms in this application shall control if they are inconsistent or contrary to the present disclosure.
The principles and embodiments of the present invention have been described herein using specific examples, which are provided only to help understand the method and the core concept of the present invention; meanwhile, for those skilled in the art, according to the idea of the present invention, there may be variations in the specific embodiments and the application scope, and in summary, the content of the present specification should not be construed as a limitation to the present invention.
Claims (8)
1. A preparation method of chitosan azelaic acid and derivatives thereof is characterized by comprising the following steps:
s1: weighing chitosan and azelaic acid according to the requirements;
s2: adding azelaic acid into purified water for dissolving, then adding sodium hydroxide, and uniformly stirring to obtain a mixed solution of azelaic acid;
s3, dissolving chitosan in purified water, adding isopropanol, stirring uniformly, and heating in water bath to obtain chitosan mixed solution;
and S4, adding the azelaic acid mixed solution into the chitosan mixed solution, cooling after uniform mixing, then carrying out vacuum filtration, and washing with acetone to obtain chitosan azelaic acid and derivatives thereof.
2. The method for preparing chitosan azelaic acid and its derivatives as claimed in claim 1, wherein in step S1, the weight ratio of chitosan to azelaic acid is 1: (1-2).
3. The method for preparing chitosan azelaic acid and its derivatives as claimed in claim 1, wherein in step S2, sodium hydroxide is added to adjust the pH of the solution to between 10-12.
4. The method for preparing chitosan azelaic acid and its derivatives as claimed in claim 1, wherein in step S3, the volume ratio of isopropanol to chitosan solution is (4-5): 1.
5. The method for preparing chitosan azelaic acid and its derivatives as claimed in claim 1, wherein the water bath heating temperature is 60-80 ℃ in step S3.
6. The method for preparing chitosan azelaic acid and its derivatives as claimed in claim 1, wherein in step S3, stirring is performed at constant temperature after heating in water bath, and the stirring time at constant temperature is 7-10 hours.
7. The application of chitosan azelaic acid and the derivatives thereof is characterized in that the chitosan azelaic acid and the derivatives thereof are used for being mixed with other acceptable ingredients to prepare cosmetics.
8. The application of chitosan azelaic acid and the derivatives thereof is characterized in that the chitosan azelaic acid and the derivatives thereof are used for preparing external medicines by mixing with other acceptable components.
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| US20010034321A1 (en) * | 2000-02-24 | 2001-10-25 | Hebert Rolland F. | Therapeutically improved salts of azelaic acid |
| CN104725530A (en) * | 2014-09-11 | 2015-06-24 | 迪沙药业集团有限公司 | Preparation method of O-carboxylated chitin |
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| US20010034321A1 (en) * | 2000-02-24 | 2001-10-25 | Hebert Rolland F. | Therapeutically improved salts of azelaic acid |
| CN104725530A (en) * | 2014-09-11 | 2015-06-24 | 迪沙药业集团有限公司 | Preparation method of O-carboxylated chitin |
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