CN115154409A - NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel and application thereof - Google Patents
NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel and application thereof Download PDFInfo
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- CN115154409A CN115154409A CN202210785609.9A CN202210785609A CN115154409A CN 115154409 A CN115154409 A CN 115154409A CN 202210785609 A CN202210785609 A CN 202210785609A CN 115154409 A CN115154409 A CN 115154409A
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Abstract
The invention discloses an NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel and application thereof. The composite hydrogel is obtained by the following steps: firstly, loading NMN by using a halloysite nano hollow tubular structure; adhering and wrapping the NMN-loaded halloysite by using a three-dimensional network structure of sodium carboxymethylcellulose molecules; finally, the twisting and stretching effect of curdlan glue in the process of gradually forming the triple-helix hydrophobic structure at 50-85 ℃ is utilized to perform twisting and interpenetration with the three-dimensional network structure of the sodium carboxymethyl cellulose to form a twisting and interpenetrating network. The pH response function of the hydrogel is realized by utilizing the pH sensitivity of carboxyl on the carboxymethyl cellulose and the characteristics that curdlan is insoluble under an acidic condition and well dissolved under an alkaline condition, and the proportion of NMN entering intestinal tracts is improved. In addition, the curdlan and the sodium carboxymethyl cellulose form a twisted interpenetrating network, so that the strength of the hydrogel is improved.
Description
Technical Field
The invention relates to the field of biomedicine, and in particular relates to a halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel loaded with NMN and application thereof.
Background
Nicotinamide Mononucleotide (NMN) is one new kind of effective antisenility functional factor reported and verified repeatedly in the journal of the New rights and the journal of the New Science, nature, cell, etc. Numerous studies have shown that under aging and various pathological conditions,intracellular NMN and coenzyme I (NAD) in mammals (including humans) + ) The levels of (c) were all greatly reduced. Under the condition of additionally supplementing NMN, the symptoms of degenerative neurological diseases (such as Alzheimer's disease) are obviously improved, the glucose tolerance of diabetic mice is improved, the recovery capability of ischemic injury of isolated heart is improved by about 30 percent compared with that of artificial spinal fluid, and in addition, the NMN also has protective effect on visual and hearing injury. The artificial injection of eNAPT vesicles which can improve the intracellular NMN level can further prolong the life of the test mice by 10.2%. Clinical reports in 2021 showed that the anti-inflammatory effect of NMN successfully reversed cytokine storm in the treatment of new coronary pneumonia, and white american women aged 55 years recovered health after 13d of drug administration. As coenzyme I (NAD) + ) NMN supplementation of NAD in humans + Has wide application prospect in the aspects of anti-aging and disease resistance. Especially under the background of severe aging of population in China and large health industry planning in Zhejiang province, the demand of the elderly population on NMN can increase year by year. How to improve the utilization rate of NMN, better maintain the health requirements of the elderly and reduce the economic pressure caused by the health requirements is very important.
The biomedical hydrogel has wide application prospect in the field of biomedicine due to good biocompatibility and good slow-release capability. Firstly, in the preparation material of hydrogel, natural polymer material becomes a main material framework due to good biocompatibility, innocuity, harmlessness, degradability and easy availability, and has good development prospect; secondly, the hydrogel is applied to the field of drug slow release, and the drug loading and slow release can be realized through the three-dimensional network structure of the hydrogel, so that the utilization rate of the drug is improved; in addition, the hydrogel has strong water absorption property, and the small mass has very large volume change after water absorption, so that the hydrogel occupies space and makes the stomach feel full in the oral application of the health care product, but does not generate too much heat to absorb, thereby having the potential of losing weight.
Disclosure of Invention
The invention aims to provide an NMN (nicotinamide mononucleotide) -loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel, a preparation method thereof and application thereof in preparing anti-aging medicaments and/or health-care products with weight-losing function.
In a first aspect, the invention provides an NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel, which is obtained by: firstly, adsorbing and loading NMN by using a halloysite nano hollow tubular structure; adhering and wrapping the halloysite loaded with the NMN by using a three-dimensional network structure of sodium carboxymethylcellulose molecules; finally, the twisting and stretching effect of curdlan glue in the process of gradually forming the triple-helix hydrophobic structure at 50-85 ℃ is utilized to perform twisting and interpenetration with the three-dimensional network structure of the sodium carboxymethyl cellulose to form a twisting and interpenetrating network.
In the process of twisting and inserting the triple-helix hydrophobic structure of curdlan and the three-dimensional network structure of sodium carboxymethylcellulose, twisting and stretching are generated inside the composite hydrogel, the halloysite inside the composite hydrogel is dispersed more uniformly, and an aggregation effect is generated; meanwhile, the mutual bonding action between the hydrogen bond on the curdlan and the hydrogen bond on the sodium carboxymethyl cellulose is generated, the intermolecular acting force is further enhanced, the halloysite can also serve as a cross-linking point, and the mechanical strength of the gel is further enhanced.
Preferably, in the composite hydrogel, the mass fraction of curdlan is 1.11-2.67%, and the mass fraction of sodium carboxymethyl cellulose is 0.11-0.22%.
Preferably, in the composite hydrogel, the mass fraction of the halloysite is 0.0022 to 0.089 percent, and the mass fraction of the NMN is 0.022 to 0.089 percent.
In a second aspect, the invention provides a preparation method of an NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel, which comprises the following specific steps:
step one, dissolving sodium carboxymethyl cellulose in distilled water to obtain sodium carboxymethyl cellulose solution.
And step two, dissolving the halloysite in distilled water to prepare a halloysite aqueous solution with the concentration of 0.1-2 mg/mL.
And step three, adding NMN into the solution obtained in the step two, stirring, and carrying out adsorption loading on the NMN by using halloysite to obtain a halloysite aqueous solution adsorbing the NMN.
And step four, dropwise adding the halloysite water solution adsorbing the NMN obtained in the step three into the sodium carboxymethyl fiber solution prepared in the step one, and stirring to obtain mixed sol.
And step five, dissolving the curdlan in an alkali solution to obtain a curdlan alkali solution with the concentration of 0.0167 g/mL-0.0267 g/mL, dripping the mixed sol obtained in the step four into the curdlan alkali solution, placing in a constant-temperature water bath at the temperature of 50-85 ℃, stirring for a certain time, and crosslinking.
Preferably, the acidity or basicity of all solutions in steps one through four is maintained at neutral.
Preferably, in the first step, the mass concentration of sodium carboxymethyl cellulose in the sodium carboxymethyl cellulose solution is 1.0-2.0%, the stirring speed in the whole process is 600-800 rpm, and the temperature is 20-70 ℃.
Preferably, in the second step, the mass concentration of the halloysite in the halloysite aqueous solution is 1 mg/mL-2 mg/mL, and the stirring speed is 300-500 rpm.
Preferably, in the third step, the concentration of the NMN in the halloysite aqueous solution for adsorbing the NMN is 1 mg/mL-4 mg/mL, the stirring speed is 200-500 rpm, and the stirring is continued for 20-30 min.
Preferably, in the fourth step, the aqueous halloysite solution adsorbing the NMN is dropwise added into the sodium carboxymethyl cellulose solution at a speed of 30-60 drops/min; continuously stirring in the dripping process, and continuously stirring for 20-40 min after the dripping is finished, wherein the stirring speed in the whole process is 600-800 rpm.
Preferably, in the fifth step, the mass concentration of the curdlan alkali solution is 0.0233 g/mL-0.0267 g/mL; continuously stirring the curdlan gum in the process of dissolving in the alkali solution, wherein the stirring speed is 600-800 rpm; the alkali solution adopts sodium hydroxide aqueous solution, and the concentration of the substance of the alkali solution is 0.0001-0.1 mol/L; when the mixed solution is dropwise added into the curdlan alkali solution, dropwise adding is needed, the dropwise adding time is controlled within 2-3 min, the stirring speed in the whole process is 600-800 rpm, and the temperature is controlled at 50-60 ℃.
In a third aspect, the invention provides an application of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel in preparation of anti-aging drugs and/or health products with a weight-losing function.
The invention has the following beneficial effects:
1. the composite hydrogel provided by the invention has good biocompatibility, is non-toxic and harmless, can be biodegraded, and has extremely high economic value and social benefit in the biomedical polymer field. The halloysite is a nano material with a hollow tubular structure, and is used for adsorbing and loading NMN to realize the first-level embedding of the NMN, and the halloysite adsorbing the NMN is redispersed in composite hydrogel formed by curdlan and sodium carboxymethylcellulose to realize the second-level embedding of the NMN; the curdlan gradually forms a triple-helix hydrophobic structure at high temperature and generates a twisting stretching effect, and is twisted and interpenetrated with the three-dimensional network structure of the sodium carboxymethyl cellulose to form a twisting interpenetrating network, so that the twisting stretching can be generated inside the composite hydrogel, and the halloysite inside the composite hydrogel is more uniformly dispersed and generates an aggregation effect; meanwhile, the hydrogen bond on the curdlan and the hydrogen bond on the sodium carboxymethyl cellulose have mutual bonding effect, so that intermolecular acting force is enhanced, the halloysite can serve as a cross-linking point between the curdlan and the sodium carboxymethyl cellulose, the mechanical strength of the gel is further enhanced, and the composite hydrogel is not easy to break in the process of passing through the esophagus and the stomach.
2. The hydrogel is prepared by compounding three natural materials, namely curdlan, sodium carboxymethylcellulose and halloysite, and the pH response function of the hydrogel is realized by utilizing the pH sensitivity of carboxyl on the carboxymethyl cellulose and the characteristics that curdlan is insoluble under an acidic condition and well soluble under an alkaline condition. In an acidic stomach environment, the composite hydrogel provided by the invention is insoluble and has low swelling property, so that the loss of NMN in the stomach is greatly reduced, and the proportion of NMN entering intestinal tracts is increased; in neutral or alkaline intestinal environment, the-COO in sodium carboxymethyl cellulose due to the alkali-soluble property of curdlan - The concentration of the hydrogel is increased, the hydrophilicity of the hydrogel is enhanced, and the three-dimensional network structure is swelled and even destroyed, thereby being beneficial to the medicineThe dissolution is carried out, so that the halloysite loaded with the NMN is exposed due to the swelling and dissolution of the hydrogel when the composite hydrogel reaches the intestinal tract, the NMN is conveniently and slowly released from the halloysite, the drug slow release function is realized, the ratio of the NMN to enter the intestinal tract and the absorption rate of the intestinal tract to the NMN are improved, the usage amount of the NMN is reduced, and the purpose of reducing the administration cost of the NMN is achieved.
3. The material used in the invention mainly comprises halloysite, sodium carboxymethylcellulose and curdlan. Curdlan is polysaccharide produced by microbial fermentation, and cannot be decomposed and utilized by enzymes of a digestion system in a human body, so that low heat is provided, and the curdlan can be applied to the field of weight-losing and health-care. The sodium carboxymethylcellulose and the halloysite are both natural materials, and after the composite hydrogel is prepared, the composite hydrogel has high water content, large water absorption volume expansion and small mass but has large volume, so that the composite hydrogel has potential application value in the field of weight reduction; meanwhile, the hydrogel has unique water absorption and retention capacity, and the volume of the hydrogel is greatly changed after water absorption, so that the hydrogel can provide a certain time of satiety in the stomach of a user. Therefore, the composite hydrogel provided by the invention can be used as a health-care product with a weight-losing function while improving the utilization rate of NMN.
Drawings
FIG. 1 is a diagram showing the mechanism of formation of a composite hydrogel
FIG. 2 is a graph comparing the NMN release quality curves of examples 1-3 under acidic conditions of the resulting composite hydrogels.
FIG. 3 is a comparison graph of NMN release quality curves of the composite hydrogels obtained in examples 1-3 under alkaline conditions.
FIG. 4 is a NMN release mass curve of the composite hydrogel obtained in example 3 under alkaline conditions for 0-1400 min.
FIG. 5 is a microscope (x 40) of a mixed sol of example 3 step five.
FIG. 6a is a micrograph (× 40) of a three-step mixed sol of example 7.
FIG. 6b is a micrograph (. Times.40) of a four-hybrid sol obtained in step IV of example 8.
FIG. 7a is a photomicrograph (X10) of a curdlan solution of example 9.
FIG. 7b is a micrograph (× 10) of a mixed solution after NMN addition in step two of example 9.
FIG. 8a is a microscopic view (25) of the sodium carboxymethylcellulose solution of example 10 step one.
FIG. 8b is a micrograph (× 25) of a mixed solution after NMN addition at step two of example 10.
FIG. 9 is a micrograph (× 40) of a three-step mixed sol of example 11.
FIG. 10 is a micrograph (× 40) of a mixed sol of step two of example 12.
FIG. 11a is a microscope (X40) of a solution of the halloysite of example 15.
Fig. 11b is a micrograph (× 40) of a mixed solution after NMN addition at step two of example 15.
Detailed Description
The invention is further described below with reference to the accompanying drawings.
Example 1
A preparation method of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan gel composite hydrogel comprises the following steps:
step one, dissolving 0.05g of sodium carboxymethylcellulose in 5mL of distilled water, heating and stirring in a water bath at 40 ℃ to prepare a sodium carboxymethylcellulose solution with the mass fraction of 1.0%.
And step two, dissolving 10mg halloysite in 10mL distilled water to prepare a 1mg/mL solution.
And step three, adding 20mgNMN into the solution obtained in the step two, and stirring for 20min.
And step four, dropwise adding the solution added in the step two into the sodium carboxymethyl fiber solution prepared in the step one at the speed of 30 drops/min, and stirring for 30min to obtain mixed sol.
And step five, dissolving 0.6g of curdlan in 30mL of sodium hydroxide solution with the substance amount concentration of 0.1mol/L to obtain 2.7% curdlan alkali solution, slowly dropwise adding the mixed solution obtained in the step four into the curdlan alkali solution for 3min, and then placing the obtained mixed system in a constant-temperature water bath at 55 ℃ for heating and stirring.
And (3) testing the embedding rate and the release amount of the composite hydrogel in an acid-base environment, wherein the initial NMN mass is 20mg in the experiment. The embedding rate of the obtained composite hydrogel for NMN is 90.5%. Placing the obtained composite hydrogel in an acidic environment (pH value =1.5, simulated stomach environment) for 90min, taking out, and placing in an alkaline environment (pH value =8, simulated intestinal environment) for 180min; the release amounts of NMN in acidic environment and alkaline environment are respectively shown in FIGS. 2 and 3; the released NMN under acidic conditions accounted for 4.74% of the total amount of gel-embedded NMN. The NMN released for 3h under the alkaline condition accounts for 1.71 percent of the total amount of the NMN embedded in the gel, and compared with the NMN in the prior art, the utilization rate of the NMN is only 0.1 percent, the utilization rate is obviously improved.
Example 2
A preparation method of NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, dissolving 0.05g of sodium carboxymethylcellulose in 5mL of distilled water, heating and stirring in a water bath at 40 ℃ to prepare a sodium carboxymethylcellulose solution with the mass fraction of 1.0%.
And step two, dissolving 4mg of halloysite in 10mL of distilled water to prepare a 0.4mg/mL solution.
And step three, adding 20mgNMN into the solution obtained in the step two, and stirring for 20min.
And step four, dropwise adding the solution added in the step two into the sodium carboxymethyl fiber solution prepared in the step one at the speed of 30 drops/min, and stirring for 30min to obtain mixed sol.
And step five, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the substance amount concentration of 0.1mol/L to obtain 2.7% curdlan alkali solution, slowly dropwise adding the mixed solution obtained in the step four into the curdlan alkali solution for 3min, and then placing the obtained mixed system in a constant-temperature water bath at 55 ℃ for heating and stirring.
And (3) testing the embedding rate and the release amount of the composite hydrogel in an acid-base environment, wherein the initial NMN mass is 20mg in the experiment. The embedding rate of the obtained composite hydrogel for NMN is 87.5%. Placing the obtained composite hydrogel in an acidic environment (pH value =1.5, simulated stomach environment) for 90min, taking out, and placing in an alkaline environment (pH value =8, simulated intestinal environment) for 180min; the release amounts of NMN in acidic environment and alkaline environment are respectively shown in figures 2 and 3; the released NMN under acidic conditions accounted for 4.50% of the total amount of gel-embedded NMN. The released NMN for 3h under alkaline conditions accounted for 0.967% of the total amount of gel-embedded NMN.
Example 3
A preparation method of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan gel composite hydrogel comprises the following steps:
step one, 0.05g of sodium carboxymethylcellulose is dissolved in 5mL of distilled water and prepared into a sodium carboxymethylcellulose solution with the mass fraction of 1.0% at normal temperature (20-25 ℃).
And step two, dissolving 20mg of halloysite in 10mL of distilled water to prepare a solution of 2 mg/mL.
And step three, adding 20mg of NMN into the solution obtained in the step two, and stirring for 30min.
And step four, dropwise adding the halloysite solution adsorbed with the NMN in the step three into the sodium carboxymethyl fiber solution prepared in the step one at a speed of 60 drops/min, and stirring for 40min to obtain mixed sol.
And step five, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the substance amount concentration of 0.001mol/L to obtain 2.7% curdlan alkali solution, slowly dropwise adding the mixed solution obtained in the step four into the curdlan alkali solution for 2min, and then placing the obtained mixed system in a constant-temperature water bath at 50 ℃ for heating and stirring.
And (3) testing the embedding rate and the release amount of the composite hydrogel in an acid-base environment, wherein the initial NMN mass is 20mg in the experiment. The embedding rate of the obtained composite hydrogel for NMN is 92.14%. Placing the obtained composite hydrogel in an acidic environment (pH value =1.5, simulated stomach environment) for 90min, taking out, and placing in an alkaline environment (pH value =8, simulated intestinal environment) for 180min; the release amounts of NMN in acidic environment and alkaline environment are respectively shown in FIGS. 2 and 3; the released NMN under acidic conditions accounted for 3.72% of the total amount of gel-loaded NMN. NMN released for 3h under alkaline conditions accounted for 1.671% of the total amount of gel-embedded NMN.
As can be seen from the comparison of the release amount of NMN in the acid-base environment of the composite hydrogel in fig. 2 and 3, the embedding effect of the composite hydrogel for NMN in example 3 is better than that in examples 1 and 2. Example 3 released less and lost less under acidic conditions than examples 1 and 2; example 3 released more in alkaline conditions than in examples 1 and 2, and therefore the intestinal availability was high. Furthermore, because the gel has a long residence time in the intestinal tract (greater than 180 min), a long-lasting sustained release can be achieved. The release amount of the gel under the alkaline condition can reach 11.69 percent of the total NMN amount by prolonging the release time to 24 hours. Analysis shows that the concentration of the halloysite is a key factor for determining the gel embedding rate, and the embedding rate is higher when the concentration of the halloysite is closer to the concentration of NMN. The relationship between the concentration of curdlan solution, the temperature and the quantity concentration of the alkaline solution is a key factor for determining the release amount of the acid and alkali coagulation. An increase in curdlan concentration decreases NMN release under acidic conditions, but inhibits NMN release under alkaline conditions when the temperature and the amount concentration of alkaline solution substances are higher.
Example 4
A preparation method of NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, dissolving 0.05g of sodium carboxymethylcellulose in 5mL of distilled water, heating and stirring in a water bath at 40 ℃, wherein the stirring speed is 600rpm, and preparing the sodium carboxymethylcellulose solution with the mass fraction of 1.0%.
And step two, dissolving 1mg of halloysite in 10mL of distilled water, and preparing a halloysite solution of 0.1mg/mL by maintaining the stirring speed at 300 rpm.
And step three, adding 10mgNMN into the halloysite solution obtained in the step two, and stirring for 30min at the stirring speed of 200rpm.
And step four, dropwise adding the NMN-adsorbed halloysite solution obtained in the step three into the sodium carboxymethyl fiber solution prepared in the step one at a speed of 30 drops/min, and stirring for 20min at a stirring speed of 600rpm to obtain a mixed sol. In the process, the carboxymethyl cellulose sodium adheres and wraps the NMN-loaded halloysite due to a three-dimensional network structure formed by the long-chair conformation.
And step five, dissolving 0.5g of curdlan in 30mL of sodium hydroxide solution with the substance amount concentration of 0.1mol/L to obtain a curdlan alkali solution with the mass fraction of 1.67%. And (3) slowly dripping the mixed solution obtained in the step four into the curdlan aqueous alkali for 2min, then placing the obtained mixed system in a constant-temperature water bath at 50 ℃, and heating and stirring for 30min to obtain the NMN-loaded composite hydrogel.
The obtained NMN-loaded composite hydrogel has poor gelling effect, shows a state that the surface is solidified but the inside is still sol, and has poor embedding effect.
Example 5
A preparation method of NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, 0.05g of sodium carboxymethylcellulose is dissolved in 5mL of distilled water and prepared into a sodium carboxymethylcellulose solution with the mass fraction of 1.0% at normal temperature (20-25 ℃).
And step two, dissolving 5mg halloysite in 10mL of distilled water to prepare a 0.5mg/mL solution.
Step three, adding 40mg of NMN into the solution obtained in the step two, and stirring for 30min.
And step four, dropwise adding the NMN-added solution obtained in the step three into the sodium carboxymethyl fiber solution prepared in the step one at the speed of 30 drops/min, and stirring for 20min to obtain mixed sol.
And step five, dissolving 0.6g of curdlan in 30mL of sodium hydroxide solution with the substance amount concentration of 0.1mol/L to obtain 2.0% curdlan alkali solution, slowly and dropwise adding the mixed solution obtained in the step four into the curdlan alkali solution for 2min, then placing the obtained mixed system in a constant-temperature water bath at 85 ℃, and heating and stirring for 30min to obtain the NMN-loaded composite hydrogel.
The embedding rate of the composite hydrogel is tested, and the initial NMN mass in the experiment is 40mg. The load rate of the obtained composite hydrogel to NMN is 79.42%. The composite gel has the advantages of hard strength, insufficient toughness and difficult tensile deformation. However, the gel is too fast because of the high temperature, resulting in the presence of bubbles in the gel.
Example 6
A preparation method of NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, dissolving 0.1g of sodium carboxymethyl cellulose in 5mL of distilled water, heating and stirring in a water bath at 70 ℃, and preparing a sodium carboxymethyl cellulose solution with the mass fraction of 2.0%.
And step two, dissolving 5mg halloysite in 10mL of distilled water to prepare a 0.5mg/mL solution.
And step three, adding 10mg of NMN into the solution obtained in the step two, and stirring for 20min.
And step four, dropwise adding the solution added in the step two into the sodium carboxymethyl cellulose solution prepared in the step one at the speed of 40 drops/min, and stirring for 20min to obtain mixed sol.
And step five, dissolving 0.7g of curdlan in 30mL of sodium hydroxide solution with the substance amount concentration of 0.01mol/L to obtain 2.3% curdlan alkali solution, slowly dropwise adding the mixed solution obtained in the step four into the curdlan alkali solution for 3min, then placing the obtained mixed system in a constant-temperature water bath at 55 ℃, and heating and stirring for 30min to obtain the NMN-loaded composite hydrogel.
The embedding rate of the composite hydrogel is tested, and the initial NMN mass in the experiment is 10mg. The loading rate of the obtained composite hydrogel to NMN is 81.34%. The gelling effect is better, and the rubber has certain toughness, but the strength is poorer than that of the rubber in the example 3.
Example 7
A preparation method of NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, 0.1g of sodium carboxymethylcellulose is dissolved in 5mL of distilled water and prepared into sodium carboxymethylcellulose solution with the mass fraction of 2.0% at normal temperature (20-25 ℃).
And step two, dissolving 10mg halloysite in 10mL distilled water to prepare a 1mg/mL solution.
And step three, dripping the solution obtained in the step two into the sodium carboxymethyl cellulose solution prepared in the step one at the speed of 30 drops/min, and stirring for 40min to obtain mixed sol.
As shown in FIG. 6a, the halloysite is uniformly dispersed in the sodium carboxymethylcellulose solution.
Example 8
A preparation method of NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, dissolving 0.05g of sodium carboxymethylcellulose in 5mL of distilled water, heating and stirring in a water bath at 50 ℃ to prepare a sodium carboxymethylcellulose solution with the mass fraction of 1.0%.
And step two, dissolving 20mg of halloysite in 10mL of distilled water to prepare a solution of 2 mg/mL.
And step three, adding 20mg of NMN into the solution obtained in the step two, and stirring for 30min.
And step four, dripping the solution prepared in the step three into the sodium carboxymethyl cellulose solution prepared in the step one at a speed of 60 drops/min, and stirring for 40min to obtain mixed sol.
As can be seen from the micrograph of the mixed sol of fig. 6b and example 8, compared with the mixed sol of fig. 6a and example 7, the original hollow round particles of example 8 are changed into solid black particles after NMN is added, which indicates that NMN is adsorbed and concentrated in the hollow pores of halloysite, and the uniform dispersion of the particles indicates that the halloysite loaded with NMN is well dispersed in the sodium carboxymethylcellulose solution.
Example 9
A preparation method of NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, 0.8g of curdlan is dissolved in 30mL of sodium hydroxide solution with the substance amount concentration of 0.1mol/L to obtain 2.7% curdlan alkali solution.
And step two, adding 20mg of NMN into the solution obtained in the step one, stirring for 20min, and then placing the obtained mixed system in a constant-temperature water bath at 55 ℃, heating and stirring.
The embedding rate of the composite hydrogel is tested, and the initial NMN mass in the experiment is 20mg. The encapsulation ratio of the obtained hydrogel in NMN was 88.23%, and it is known from fig. 7a and 7b that addition of NMN to a solution of curdlan causes local aggregation of curdlan. The result shows that the pure curdlan has a certain embedding effect on the NMN, but the effect is not obvious, and the uniform dispersion of the medicine is not facilitated.
Example 10
Step one, 0.05g of sodium carboxymethylcellulose is dissolved in 5mL of distilled water and prepared into a sodium carboxymethylcellulose solution with the mass fraction of 1.0% at normal temperature (20-25 ℃).
Step two, adding 20mgNMN into the solution in the step one, and stirring for 20min.
Figure 8a,8b can know, pure carboxymethyl cellulose for NMN embedding effect is not good. And the sodium carboxymethylcellulose has poor gelling effect and shows certain fluidity. Therefore, pure sodium carboxymethyl cellulose is not a support material for preparing the composite gel, and the relationship between the gelling property and the mechanical strength of the gel and the sodium carboxymethyl cellulose is not large.
Example 11
Step one, 0.05g of sodium carboxymethyl cellulose is dissolved in 5mL of distilled water, and the sodium carboxymethyl cellulose solution with the mass fraction of 1.0 percent is prepared at normal temperature (20-25 ℃).
And step two, adding 20mg of NMN into the solution in the step two, and stirring for 20min.
And step three, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the substance amount concentration of 0.1mol/L to obtain 2.7% curdlan alkali solution, slowly dropwise adding the mixed solution obtained in the step two into the curdlan alkali solution for 3min, and then placing the obtained mixed system in a thermostatic water bath at 55 ℃ for heating and stirring.
The embedding rate of the composite hydrogel is tested, and the initial NMN mass in the experiment is 20mg. The embedding rate of the obtained composite hydrogel for NMN is 72.44%, compared with example 10, the hydrogel can be formed by adding curdlan and cooling at normal temperature, and the hydrogel has a good gelling effect and certain elasticity. The water-holding capacity of the gel becomes stronger after the addition of carboxymethyl cellulose as compared with that of example 9, and after one day of storage at low temperature (5 to 10 ℃), water exudes already in example 9, but the water exudes no more than three days of storage under the same conditions. The curdlan plays a critical role in the gel forming property of the gel, and the water locking performance of the gel can be further improved by adding the sodium carboxymethyl cellulose.
Example 12
Step one, 0.05g of sodium carboxymethylcellulose is dissolved in 5mL of distilled water and prepared into a sodium carboxymethylcellulose solution with the mass fraction of 1.0% at normal temperature (20-25 ℃).
And step two, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the substance amount concentration of 0.1mol/L to obtain 2.7% curdlan alkali solution, slowly dropwise adding the sodium carboxymethyl cellulose solution obtained in the step one into the curdlan alkali solution for 3min, and then placing the obtained mixed system in a constant-temperature water bath at 55 ℃ for heating and stirring.
Fig. 5, 9 and 10 are microscope images respectively showing the mixed solutions of examples 3, 11 and 12, and it can be observed from fig. 10 that the mixed sol of carboxymethyl cellulose and curdlan is uniformly dispersed before NMN is added, fig. 9 shows that the mixed sol after NMN is added, the particles of fig. 10 become larger, the structure is changed, and the structure is connected into a plurality of sheet structures, fig. 5 shows that the mixed sol after halloysite is added, and the particle structure is more black than fig. 9 and fig. 10. The halloysite plays a main role in adsorption and enrichment of NMN and has an important influence on the embedding rate of the composite hydrogel on the NMN.
Example 13
Step one, 40mg halloysite is dissolved in 10mL distilled water to prepare a 2mg/mL solution.
And step two, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the substance amount concentration of 0.001mol/L to obtain 2.7% curdlan alkali solution, slowly dropwise adding the solution obtained in the step one into the curdlan alkali solution for 2min, and then placing the obtained mixed system in a constant-temperature water bath at 50 ℃ for heating and stirring.
Example 14
Step one, 40mg halloysite is dissolved in 10mL distilled water to prepare a 2mg/mL solution.
And step two, adding 20mg of NMN into the solution obtained in the step one, and stirring for 20min.
And step three, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the substance amount concentration of 0.001mol/L to obtain 2.7% curdlan alkali solution, slowly dropwise adding the solution obtained in the step two into the curdlan alkali solution for 2min, and then placing the obtained mixed system in a constant-temperature water bath at 50 ℃ for heating and stirring.
The embedding rate of the composite hydrogel is tested, and the initial NMN mass in the experiment is 20mg. The embedding rate of the obtained hydrogel for NMN is 88.90%.
Example 15
Step one, 20mg halloysite is dissolved in 10mL distilled water to prepare a 2mg/mL solution.
And step two, adding 20mg of NMN into the solution in the step two, and stirring for 30min.
Fig. 11a and 11b are respectively a microscope image of the halloysite solution obtained in the first step of example 15 and a microscope image of the mixed solution after NMN is added in the second step of example 15, so that it can be seen that the pure halloysite solution in the first step of example 15 (fig. 11 a) is dispersed and hollow dots, and the mixed solution after NMN is added in the second step of example 15 (fig. 11 b) has some agglomerated black lumps, which indicates that the halloysite has the effect of embedding and enriching the NMN. Compared with the mixed solution of example 8 shown in fig. 6b, the NMN embedding effect of example 8 is better, and the drug is dispersed more uniformly after the sodium carboxymethyl cellulose is added. Therefore, the sodium carboxymethyl cellulose plays a role of a uniform medium in the system, so that the medicine is uniformly dispersed in the gel, and the problems of excessive medicine and insufficient dosage in the use process of the medicine are avoided.
Claims (10)
1. The NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan gel composite hydrogel is characterized in that: obtained by the following method: firstly, loading NMN by using a halloysite nano hollow tubular structure; adhering and wrapping the halloysite loaded with the NMN by using a three-dimensional network structure of sodium carboxymethylcellulose molecules; finally, the twisting and stretching effect of curdlan glue in the process of gradually forming the triple-helix hydrophobic structure at 50-85 ℃ is utilized to perform twisting and interpenetration with the three-dimensional network structure of the sodium carboxymethyl cellulose to form a twisting and interpenetrating network.
2. The NMN loaded halloysite/sodium carboxymethylcellulose/curdlan hydrogel according to claim 1, wherein the NMN loaded halloysite/sodium carboxymethylcellulose/curdlan hydrogel comprises: the mass fraction of curdlan is 1.11-2.67%, and the mass fraction of sodium carboxymethylcellulose is 0.11-0.22%.
3. The NMN loaded halloysite/sodium carboxymethylcellulose/curdlan hydrogel according to claim 1, wherein the NMN loaded halloysite/sodium carboxymethylcellulose/curdlan hydrogel comprises: the halloysite accounts for 0.0022 to 0.089 percent by mass, and the NMN accounts for 0.022 to 0.089 percent by mass.
4. The method for preparing the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel according to claim 1, wherein the method comprises the following steps: the method comprises the following steps: dissolving sodium carboxymethylcellulose in distilled water to obtain a sodium carboxymethyl cellulose solution;
dissolving halloysite in distilled water to prepare a halloysite water solution with the concentration of 0.1-2 mg/mL;
step three, adding NMN into the solution obtained in the step two, stirring, and carrying out adsorption loading on the NMN by using halloysite to obtain a halloysite aqueous solution adsorbing the NMN;
step four, dropwise adding the halloysite water solution adsorbing the NMN obtained in the step three into the sodium carboxymethyl fiber solution prepared in the step one, and stirring to obtain mixed sol;
and step five, dissolving the curdlan in an alkali solution to obtain a curdlan alkali solution with the concentration of 0.0167 g/mL-0.0267 g/mL, dripping the mixed sol obtained in the step four into the curdlan alkali solution, placing in a constant-temperature water bath at the temperature of 50-85 ℃, stirring for a certain time, and crosslinking.
5. The method of claim 4, wherein: the acid-base property of all solutions in the first to fourth steps is kept neutral.
6. The method of claim 4, wherein: in the first step, the mass concentration of sodium carboxymethyl cellulose in the sodium carboxymethyl cellulose solution is 1.0-2.0%, the stirring speed in the whole process is 600-800 rpm, and the temperature is 20-70 ℃.
7. The method of manufacturing according to claim 4, characterized in that: in the second step, the mass concentration of the halloysite in the halloysite aqueous solution is 1 mg/mL-2 mg/mL, and the stirring speed is 300-500 rpm; in the third step, the concentration of NMN in the halloysite aqueous solution for adsorbing NMN is 1-4 mg/mL, the stirring speed is 200-500 rpm, and the stirring is continued for 20-30 min.
8. The method of claim 4, wherein: in the fourth step, the halloysite water solution adsorbing the NMN is dropwise added into the sodium carboxymethyl cellulose solution at the speed of 30-60 drops/min; continuously stirring in the dripping process, and continuously stirring for 20-40 min after the dripping is finished, wherein the stirring speed in the whole process is 600-800 rpm.
9. The method of claim 4, wherein: in the fifth step, the mass concentration of the curdlan alkali solution is 0.0233 g/mL-0.0267 g/mL; continuously stirring the curdlan gum in the process of dissolving in the alkali solution, wherein the stirring speed is 600-800 rpm; the alkali solution is sodium hydroxide aqueous solution, and the concentration of the alkali solution is 0.0001-0.1 mol/L; when the mixed solution is dropwise added into the curdlan alkali solution, dropwise adding is needed, the dropwise adding time is controlled within 2-3 min, the stirring speed in the whole process is 600-800 rpm, and the temperature is controlled at 50-60 ℃.
10. The use of the NMN loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel according to claim 1 in the preparation of anti-aging drugs and/or health products with weight-losing function.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103520113A (en) * | 2012-07-03 | 2014-01-22 | 中国科学院兰州化学物理研究所 | Halloysite nano composite gel microspheres and preparation method thereof |
| WO2017084300A1 (en) * | 2015-11-20 | 2017-05-26 | 清华大学 | Hyaluronic acid-methyl cellulose composite gel, and preparation and application thereof |
| CN106983868A (en) * | 2017-03-29 | 2017-07-28 | 中南大学 | A kind of preparation method of halloysite nanotubes pharmaceutical carrier and halloysite nanotubes carrier medicament |
| KR20190080189A (en) * | 2017-12-28 | 2019-07-08 | 낙우산업(주) | Ecofriendly natural paint using halloysite nano tube and the preparing process the same |
| CN110041537A (en) * | 2019-04-24 | 2019-07-23 | 上海交通大学 | A kind of ionomer carboxymethyl curdlan gum physical hydrogel and preparation method thereof |
| KR20200007747A (en) * | 2018-07-12 | 2020-01-22 | 순천향대학교 산학협력단 | A chitosan/TEMPO oxidized cellulose nanofiber hydrogel comprising fk506 for bone therapy and a method for manufacturing the same |
| CN112795058A (en) * | 2021-01-08 | 2021-05-14 | 杭州师范大学钱江学院 | Curdlan/halloysite composite hydrogel and application and preparation method thereof |
-
2022
- 2022-07-04 CN CN202210785609.9A patent/CN115154409B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103520113A (en) * | 2012-07-03 | 2014-01-22 | 中国科学院兰州化学物理研究所 | Halloysite nano composite gel microspheres and preparation method thereof |
| WO2017084300A1 (en) * | 2015-11-20 | 2017-05-26 | 清华大学 | Hyaluronic acid-methyl cellulose composite gel, and preparation and application thereof |
| CN106983868A (en) * | 2017-03-29 | 2017-07-28 | 中南大学 | A kind of preparation method of halloysite nanotubes pharmaceutical carrier and halloysite nanotubes carrier medicament |
| KR20190080189A (en) * | 2017-12-28 | 2019-07-08 | 낙우산업(주) | Ecofriendly natural paint using halloysite nano tube and the preparing process the same |
| KR20200007747A (en) * | 2018-07-12 | 2020-01-22 | 순천향대학교 산학협력단 | A chitosan/TEMPO oxidized cellulose nanofiber hydrogel comprising fk506 for bone therapy and a method for manufacturing the same |
| CN110041537A (en) * | 2019-04-24 | 2019-07-23 | 上海交通大学 | A kind of ionomer carboxymethyl curdlan gum physical hydrogel and preparation method thereof |
| CN112795058A (en) * | 2021-01-08 | 2021-05-14 | 杭州师范大学钱江学院 | Curdlan/halloysite composite hydrogel and application and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| KEQIN WANG等: ""Preparation of chitosan/curdlan/carboxymethyl cellulose blended film and its characterization"", 《J FOOD SCI TECHNOL》, vol. 56, pages 5396 - 5404, XP036930570, DOI: 10.1007/s13197-019-04010-2 * |
| YUCHENG LI 等: ""Synthesis and characterization of curdlan/β-cyclodextrin composite hydrogels for sustained-release"", 《INTERNATIONAL JOURNAL OF POLYMERIC MATERIALS AND POLYMERIC BIOMATERIALS》, vol. 68, no. 13, pages 778 - 787 * |
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