CN115154409B - 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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- CN115154409B CN115154409B CN202210785609.9A CN202210785609A CN115154409B CN 115154409 B CN115154409 B CN 115154409B CN 202210785609 A CN202210785609 A CN 202210785609A CN 115154409 B CN115154409 B CN 115154409B
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Abstract
The invention discloses NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel and application thereof. The composite hydrogel is obtained by the following method: firstly, adsorbing and loading NMN by utilizing a halloysite nano hollow tubular structure; then, adhering and wrapping the halloysite loaded with NMN by utilizing a three-dimensional network structure of sodium carboxymethyl cellulose molecules; and finally, utilizing the torsion stretching effect of the curdlan in the process of gradually forming a triple-helix hydrophobic structure at 50-85 ℃ to carry out torsion penetration with a three-dimensional network structure of sodium carboxymethyl cellulose so as to form a torsion interpenetrating network. The invention utilizes the pH sensitivity of carboxyl on carboxymethyl cellulose and the characteristic that the curdlan is insoluble under acidic condition and is well dissolved under alkaline condition to realize the pH response function of the hydrogel, thereby improving the proportion of NMN entering intestinal tracts. In addition, the curdlan and the sodium carboxymethyl cellulose form a torsion interpenetrating network, so that the strength of the hydrogel is improved.
Description
Technical Field
The invention relates to the biomedical field, in particular to NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel and application thereof.
Background
Nicotinamide Mononucleotide (NMN) is a novel anti-aging functional factor which is effective in repeated report and repeated verification on authoritative journals such as Science, nature, cell and the like and sub-journals thereof in recent years. Numerous studies have shown that NMN and coenzyme I (NAD) are found in mammalian (including human) somatic cells under aging and a variety of pathological conditions + ) The level of (c) is greatly reduced. Under the condition of additionally supplementing NMN, the symptoms of degenerative nerve diseases (such as Alzheimer's syndrome) are obviously improved, the glucose tolerance of a diabetic mouse is improved, the recovery capacity of the isolated heart ischemic injury is improved by about 30 percent compared with that of the artificial spinal fluid, and in addition, the NMN has a protective effect on vision and hearing injury. Artificial injection of ennampt vesicles to increase intracellular NMN levels further increases test mice longevity by 10.2Percent of the total weight of the composition. Clinical report 2021 shows that the anti-inflammatory effect of NMN successfully reverses cytokine storm in the treatment of novel coronavirus infection, and the white us female patient aged 55 years after 13d of administration is healed. As coenzyme I (NAD) + ) NMN supplements NAD in humans + Has wide application prospect in the aspects of anti-aging and disease resistance. Especially, in the background of serious aging of population in China and large healthy industry planning in Zhejiang province, the NMN demand of the aged population can be increased year by year. How to improve the utilization rate of NMN, it is important to better maintain the health requirement of the old people and to alleviate the economic pressure caused by the health requirement.
The biomedical hydrogel has a wide application prospect in the biomedical field due to good biocompatibility and good slow release capability. Firstly, in the preparation materials of the hydrogel, the natural polymer material has good biological compatibility, no toxicity and harmlessness, degradability and availability as main material framework, and has good development prospect; secondly, the hydrogel is applied to the field of medicine slow release, and the loading and slow release of the medicine can be realized through the three-dimensional network structure of the hydrogel, so that the medicine utilization rate is improved; in addition, the hydrogel has very large volume change after absorbing water with small mass because of strong water absorption property, and has great weight-losing potential because the hydrogel occupies space and can not generate too much heat absorption although the stomach is full in oral application of the health care product.
Disclosure of Invention
The invention aims to provide NMN (nicotinamide mononucleotide) -loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel, a preparation method thereof and application thereof in preparing anti-aging drugs and/or health-care products with a weight-losing function.
In a first aspect, the present invention provides an NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel, which is obtained by: firstly, adsorbing and loading NMN by utilizing a halloysite nano hollow tubular structure; then, adhering and wrapping the halloysite loaded with NMN by utilizing a three-dimensional network structure of sodium carboxymethyl cellulose molecules; and finally, utilizing the torsion stretching effect of the curdlan in the process of gradually forming a triple-helix hydrophobic structure at 50-85 ℃ to carry out torsion penetration with a three-dimensional network structure of sodium carboxymethyl cellulose so as to form a torsion interpenetrating network.
In the process of twisting and inserting the triple-helix hydrophobic structure of the curdlan and the three-dimensional network structure of the sodium carboxymethylcellulose, twisting and stretching are generated in the composite hydrogel, and halloysite in the composite hydrogel is dispersed more uniformly and an aggregation effect is generated; meanwhile, the hydrogen bond on the curdlan and the hydrogen bond on the sodium carboxymethylcellulose have mutual bonding action, so that the acting force between molecules is further enhanced, halloysite can serve as a crosslinking point, and the mechanical strength of the gel is further enhanced.
Preferably, in the composite hydrogel, the mass fraction of the curdlan is 1.11-2.67%, and the mass fraction of the sodium carboxymethyl cellulose is 0.11-0.22%.
Preferably, in the composite hydrogel, the mass fraction of halloysite is 0.0022% -0.089%, and the mass fraction of NMN is 0.022% -0.089%.
In a second aspect, the invention provides a preparation method of 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 secondly, dissolving halloysite in distilled water to prepare a halloysite aqueous solution with the concentration of 0.1 mg/mL-2 mg/mL.
And thirdly, adding NMN into the solution obtained in the second step, stirring, and carrying out adsorption loading on the NMN by using halloysite to obtain a halloysite aqueous solution for adsorbing the NMN.
And step four, dripping the halloysite aqueous solution for adsorbing NMN obtained in the step three into the sodium carboxymethyl cellulose solution prepared in the step one, and stirring to obtain mixed sol.
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 the curdlan alkali solution in a constant-temperature water bath with the temperature of 50-85 ℃, and stirring for a certain time to crosslink.
Preferably, the acid-base properties of all the solutions in steps one to four are maintained at neutrality.
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 is 600-800 rpm in the whole process, and the temperature is 20-70 ℃.
Preferably, in the second step, the mass concentration of 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 NMN in the halloysite aqueous solution for adsorbing NMN is 1 mg/mL-4 mg/mL, the stirring speed is 200-500 rpm, and stirring is continued for 20-30 min.
Preferably, in the fourth step, dropwise adding is adopted in the process of dropwise adding the halloysite aqueous solution for adsorbing NMN into the sodium carboxymethyl cellulose solution, wherein the dropwise adding speed is 30-60 drops/min; stirring is continuously carried out in the dripping process, and stirring is continuously carried out 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 process of dissolving the curdlan in the alkali solution, wherein the stirring speed is 600-800 rpm; the aqueous alkali adopts sodium hydroxide aqueous solution, and the concentration of the substance of the aqueous alkali is 0.0001 mol/L-0.1 mol/L; when the mixed solution is dripped into the curdlan alkali solution, the mixed solution is required to be added dropwise, the dripping time is controlled to be within 2-3 min, the stirring speed is 600-800 rpm in the whole process, and the temperature is controlled to be 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-care products with a weight-losing function.
The invention has the beneficial effects that:
1. the composite hydrogel provided by the invention has good biocompatibility, is nontoxic and harmless, can be biodegraded, and has extremely high economic value and social benefit in the biomedical polymer field. Halloysite is a nano material with a hollow tubular structure, NMN is adsorbed and loaded by the halloysite, so that first-level embedding of NMN is realized, and the halloysite adsorbed with NMN is redispersed in composite hydrogel formed by curdlan and sodium carboxymethyl cellulose, so that second-level embedding of NMN is realized; the triple helix hydrophobic structure is gradually formed and a torsion stretching effect is generated at high temperature by the curdlan, and the triple helix hydrophobic structure is twisted and inserted with the three-dimensional network structure of the sodium carboxymethyl cellulose to form a torsion interpenetrating network, so that the torsion stretching can be generated in the composite hydrogel, and the halloysite in the composite hydrogel can be uniformly dispersed and a gathering effect can be generated; meanwhile, the hydrogen bond on the curdlan and the hydrogen bond on the sodium carboxymethyl cellulose have mutual bonding action, so that the acting force between molecules is enhanced, halloysite can serve as a crosslinking 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 esophagus and stomach.
2. The invention uses three natural materials of curdlan, sodium carboxymethyl cellulose and halloysite to compound and prepare hydrogel, and utilizes the pH sensitivity of carboxyl on carboxymethyl cellulose and the characteristic that the curdlan is insoluble under acidic condition and well soluble under alkaline condition to realize the pH response function of the hydrogel. 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 the intestinal tract is improved; in neutral or alkaline intestinal tract environment, sodium carboxymethylcellulose has-COO due to alkali dissolution property of curdlan - The concentration of the composite hydrogel is increased, the hydrophilicity of the hydrogel is enhanced, the three-dimensional network structure is swelled or even destroyed, and the dissolution of the medicine is facilitated, so that the halloysite loaded with NMN is exposed due to the swelling and the dissolution of the hydrogel when the composite hydrogel reaches the intestinal tract, the NMN is conveniently slowly released from the halloysite, the medicine slow-release function is realized, the proportion of the NMN entering the intestinal tract is improved, the absorption rate of the intestinal tract to the NMN is improved, the use amount of the NMN is reduced, and the aim of reducing the administration cost of the NMN is fulfilled.
3. The materials used in the invention mainly comprise halloysite, sodium carboxymethyl cellulose and curdlan. The curdlan is polysaccharide produced by microbial fermentation, and can not be decomposed and utilized by enzymes of the digestive system in human bodies, so that the curdlan has low heat, and can be applied to the field of weight losing and health care. The sodium carboxymethylcellulose and halloysite are natural materials, and after the composite hydrogel is prepared, the water content is high, the volume expansion of water absorption is large, the smaller mass has larger volume, and the composite hydrogel has potential application value in the field of weight loss; meanwhile, the hydrogel has unique water absorption and water retention capacity, the volume of the hydrogel changes greatly after water absorption, and the hydrogel can provide a period 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 the weight-losing function while improving the NMN utilization rate.
Drawings
FIG. 1 is a diagram showing the mechanism of formation of a composite hydrogel
FIG. 2 is a graph showing NMN release mass curves of examples 1-3 under acidic conditions of the resulting composite hydrogels.
FIG. 3 is a graph showing NMN release mass curves of the composite hydrogels obtained in examples 1 to 3 under alkaline conditions.
FIG. 4 is a graph showing NMN release quality of the composite hydrogel obtained in example 3 under alkaline conditions for 0-1400 min.
FIG. 5 is a microscope image of a five step hybrid sol (x 40) of example 3.
FIG. 6a is a microscope image of a step three hybrid sol of example 7 (x 40).
FIG. 6b is a microscope image of the step four hybrid sol of example 8 (x 40).
FIG. 7a is a microscopic view of the step one curdlan solution of example 9 (. Times.10).
FIG. 7b is a microscopic image (10) of the mixed solution after NMN addition in step two of example 9.
FIG. 8a is a microscopic view of sodium carboxymethyl cellulose solution (x 25) of the step of example 10.
FIG. 8b is a microscopic image (x 25) of the mixed solution after NMN addition in step two of example 10.
FIG. 9 is a step three hybrid sol micrograph (40) of example 11.
FIG. 10 is a microscope image of the step two hybrid sol of example 12 (x 40).
FIG. 11a is a microscopic view of a halloysite solution (x 40) at step one of example 15.
FIG. 11b is a microscopic image (x 40) of the mixed solution after NMN addition in step two of example 15.
Detailed Description
The invention is further described below with reference to the accompanying drawings.
Example 1
The preparation method of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, dissolving 0.05g of sodium carboxymethyl cellulose in 5mL of distilled water, and heating and stirring in a water bath at 40 ℃ to prepare a sodium carboxymethyl cellulose solution with the mass fraction of 1.0%.
Step two, 10mg halloysite is dissolved 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 fourthly, dripping the NMN-added 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 30min to obtain the mixed sol.
And fifthly, dissolving 0.6g of curdlan in 30mL of sodium hydroxide solution with the mass 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.
The composite hydrogel was tested for entrapment rate and release in acid-base environment, with an initial NMN mass of 20mg in the experiment. The embedding rate of the obtained composite hydrogel for NMN is 90.5%. The obtained composite hydrogel is firstly placed in an acidic environment (pH value=1.5, stomach environment is simulated) for 90min, and then is placed in an alkaline environment (pH value=8, intestinal environment is simulated) for 180min after being taken out; the release amounts of NMN in the acidic environment and the alkaline environment are shown in figures 2 and 3 respectively; the NMN released under acidic conditions was 4.74% of the total NMN embedded in the gel. The NMN released for 3h under alkaline condition accounts for 1.71% of the total NMN embedded in the gel, and compared with the prior art, the utilization rate of only 0.1% of NMN is obviously improved.
Example 2
The preparation method of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, dissolving 0.05g of sodium carboxymethyl cellulose in 5mL of distilled water, and heating and stirring in a water bath at 40 ℃ to prepare a sodium carboxymethyl cellulose solution with the mass fraction of 1.0%.
Step two, 4mg halloysite is dissolved in 10mL distilled water to prepare 0.4mg/mL solution.
And step three, adding 20mgNMN into the solution obtained in the step two, and stirring for 20min.
And fourthly, dripping the NMN-added 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 30min to obtain the mixed sol.
And fifthly, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the mass 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.
The composite hydrogel was tested for entrapment rate and release in acid-base environment, with an initial NMN mass of 20mg in the experiment. The embedding rate of the obtained composite hydrogel for NMN is 87.5%. The obtained composite hydrogel is firstly placed in an acidic environment (pH value=1.5, stomach environment is simulated) for 90min, and then is placed in an alkaline environment (pH value=8, intestinal environment is simulated) for 180min after being taken out; the release amounts of NMN in the acidic environment and the alkaline environment are shown in figures 2 and 3 respectively; the NMN released under acidic conditions was 4.50% of the total NMN embedded in the gel. The NMN released for 3h under alkaline conditions was 0.967% of the total NMN embedded in the gel.
Example 3
The preparation method of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, dissolving 0.05g of sodium carboxymethyl cellulose in 5mL of distilled water, and preparing sodium carboxymethyl cellulose solution with the mass fraction of 1.0% at normal temperature (20-25 ℃).
Step two, 20mg halloysite is dissolved in 10mL distilled water to prepare a 2mg/mL solution.
And thirdly, adding 20mgNMN into the solution obtained in the second step, and stirring for 30min.
And step four, dripping the halloysite solution adsorbed with NMN in the step three into the sodium carboxymethyl cellulose solution prepared in the step one at the speed of 60 drops/min, and stirring for 40min to obtain mixed sol.
And fifthly, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the mass 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.
The composite hydrogel was tested for entrapment rate and release in acid-base environment, with an initial NMN mass of 20mg in the experiment. The embedding rate of the obtained composite hydrogel for NMN is 92.14%. The obtained composite hydrogel is firstly placed in an acidic environment (pH value=1.5, stomach environment is simulated) for 90min, and then is placed in an alkaline environment (pH value=8, intestinal environment is simulated) for 180min after being taken out; the release amounts of NMN in the acidic environment and the alkaline environment are shown in figures 2 and 3 respectively; the NMN released under acidic conditions represents 3.72% of the total NMN loaded on the gel. The NMN released under alkaline conditions for 3h accounted for 1.671% of the total NMN embedded in the gel.
As can be seen from the comparison of the release amounts of NMN in the acid-base environment of the composite hydrogel in fig. 2 and 3, the embedding effect of example 3 on NMN is better than that of examples 1 and 2. Example 3 released less amount under acidic conditions and less loss than examples 1 and 2; example 3 has a higher release rate under alkaline conditions than examples 1 and 2, and thus has a high intestinal tract utilization. In addition, because the residence time of the gel in the intestine is long (greater than 180 min), a long-lasting sustained release can be achieved. The release time is prolonged to 24 hours, and the release amount of the gel under alkaline conditions can reach 11.69% of the total NMN. Analysis shows that the concentration of halloysite is a key factor for determining the gel entrapment rate, and the entrapment rate is higher when the concentration of halloysite is closer to the NMN concentration. The relationship between the concentration of the curdlan gum solution, the temperature and the concentration of the alkaline solution is a key factor for determining the release amount of the gel base. An increase in the concentration of the curdlan decreases the release of NMN under acidic conditions, but inhibits the release of NMN under alkaline conditions when the temperature and the concentration of the alkaline solution substance are higher.
Example 4
The preparation method of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, 0.05g of sodium carboxymethyl cellulose is dissolved in 5mL of distilled water, and the solution is heated and stirred in a water bath at 40 ℃ at a stirring speed of 600rpm to prepare sodium carboxymethyl cellulose solution with a mass fraction of 1.0%.
Step two, 1mg of halloysite was dissolved in 10mL of distilled water, and a stirring speed was maintained at 300rpm to prepare a halloysite solution of 0.1 mg/mL.
And thirdly, adding 10mgNMN into the halloysite solution obtained in the second step, and stirring for 30min at the stirring speed of 200rpm.
And step four, dripping the halloysite solution with the NMN adsorbed obtained in the step three into the sodium carboxymethyl cellulose solution prepared in the step one at the speed of 30 drops/min, and stirring for 20min at the stirring speed of 600rpm to obtain mixed sol. In the process, sodium carboxymethyl cellulose adheres and wraps halloysite loaded with NMN due to a three-dimensional network structure formed by a bench-type conformation.
And fifthly, dissolving 0.5g of curdlan in 30mL of sodium hydroxide solution with the mass concentration of 0.1mol/L to obtain the curdlan alkali solution with the mass fraction of 1.67%. Slowly dripping 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 50 ℃, heating and stirring for 30min, and obtaining the NMN-loaded composite hydrogel.
The obtained NMN-loaded composite hydrogel has poor gel forming effect, presents a state of surface solidification but internal sol, and has poor embedding effect.
Example 5
The preparation method of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, dissolving 0.05g of sodium carboxymethyl cellulose in 5mL of distilled water, and preparing sodium carboxymethyl cellulose solution with the mass fraction of 1.0% at normal temperature (20-25 ℃).
Step two, 5mg halloysite is dissolved in 10mL distilled water to prepare 0.5mg/mL solution.
And thirdly, adding 40mgNMN into the solution obtained in the second step, and stirring for 30min.
And step four, dropwise adding the NMN-added solution obtained in the step three into the sodium carboxymethyl cellulose solution prepared in the step one at the speed of 30 drops/min, and stirring for 20min to obtain the mixed sol.
And fifthly, dissolving 0.6g of curdlan in 30mL of sodium hydroxide solution with the mass concentration of 0.1mol/L to obtain 2.0% of 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 85 ℃, heating and stirring for 30min to obtain the NMN-loaded composite hydrogel.
The composite hydrogel was tested for entrapment rate with an initial NMN mass of 40mg in the experiment. The loading rate of the obtained composite hydrogel to NMN is 79.42%. The composite gel has harder strength, but insufficient toughness, and is not easy to stretch and deform. However, because the temperature is too high, the gel is formed too quickly, so that bubbles exist in the gel.
Example 6
The preparation method of the 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, and heating and stirring in a water bath at 70 ℃ to prepare a sodium carboxymethyl cellulose solution with the mass fraction of 2.0%.
Step two, 5mg halloysite is dissolved in 10mL distilled water to prepare 0.5mg/mL solution.
And thirdly, adding 10mgNMN into the solution obtained in the second step, and stirring for 20min.
And fourthly, dripping the NMN-added solution obtained 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 the mixed sol.
And fifthly, dissolving 0.7g of curdlan in 30mL of sodium hydroxide solution with the mass concentration of 0.01mol/L to obtain 2.3% of 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 ℃, heating and stirring for 30min to obtain the NMN-loaded composite hydrogel.
The composite hydrogel was tested for entrapment rate with an initial NMN mass of 10mg in the experiment. The loading rate of the obtained composite hydrogel to NMN is 81.34%. The gel forming effect is better, and the gel forming agent has certain toughness, but the strength is poorer than that of the example 3.
Example 7
The preparation method of the 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, and preparing sodium carboxymethyl cellulose solution with mass fraction of 2.0% at normal temperature (20-25 ℃).
Step two, 10mg halloysite is dissolved in 10mL distilled water to prepare a 1mg/mL solution.
And thirdly, dropwise adding the solution obtained in the second step into the sodium carboxymethyl cellulose solution prepared in the first step at the speed of 30 drops/min, and stirring for 40min to obtain the mixed sol.
As shown in fig. 6a, halloysite is uniformly dispersed in the solution of sodium carboxymethyl cellulose.
Example 8
The preparation method of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, dissolving 0.05g of sodium carboxymethyl cellulose in 5mL of distilled water, and heating and stirring in a water bath at 50 ℃ to prepare a sodium carboxymethyl cellulose solution with the mass fraction of 1.0%.
Step two, 20mg halloysite is dissolved in 10mL distilled water to prepare a 2mg/mL solution.
And thirdly, adding 20mgNMN into the solution obtained in the second step, and stirring for 30min.
And step four, dropwise adding the solution prepared in the step three into the sodium carboxymethyl cellulose solution prepared in the step one at the speed of 60 drops/min, and stirring for 40min to obtain the mixed sol.
As can be seen from the microscopic image shown in the mixed sol of example 8 in fig. 6b, compared with the mixed sol of example 7 in fig. 6a, in example 8, after NMN is added, the original hollow round particles become solid black particles, which indicates that NMN is adsorbed and enriched in the hollow holes of halloysite, and even dispersion of the particles indicates that the halloysite loaded with NMN is better dispersed in sodium carboxymethyl cellulose solution.
Example 9
The preparation method of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel comprises the following steps:
step one, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the mass 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 ℃, and heating and stirring.
The composite hydrogel was tested for entrapment rate with an initial NMN mass of 20mg in the experiment. The embedding rate of the obtained hydrogel for NMN is 88.23%, and as shown in FIGS. 7a and 7b, the NMN can cause local agglomeration of the Kelde gum after being added with the Kelde gum solution. The simple curdlan has a certain embedding effect on NMN, but the effect is not obvious, and the uniform dispersion of the medicine is not facilitated.
Example 10
Step one, dissolving 0.05g of sodium carboxymethyl cellulose in 5mL of distilled water, and preparing sodium carboxymethyl cellulose solution with the mass fraction of 1.0% at normal temperature (20-25 ℃).
And step two, adding 20mgNMN into the solution in the step one, and stirring for 20min.
FIGS. 8a and 8b show that pure carboxymethylcellulose has poor NMN-embedding effect. And the sodium carboxymethylcellulose has poor gelling effect and shows certain fluidity. Therefore, pure sodium carboxymethyl cellulose is not a supporting material for preparing composite gel, and the gel forming property and mechanical strength of the gel are not greatly related to sodium carboxymethyl cellulose.
Example 11
Step one, dissolving 0.05g of sodium carboxymethyl cellulose in 5mL of distilled water at normal temperature (20-25 ℃) to prepare sodium carboxymethyl cellulose solution with the mass fraction of 1.0%.
And step two, adding 20mgNMN into the solution obtained in the step two, and stirring for 20min.
And thirdly, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the mass concentration of 0.1mol/L to obtain 2.7% curdlan alkali solution, slowly dripping the mixed solution obtained in the second step into the curdlan alkali solution for 3min, and then placing the obtained mixed system in a constant-temperature water bath with the temperature of 55 ℃ for heating and stirring.
The composite hydrogel was tested for entrapment rate with an initial NMN mass of 20mg in the experiment. Compared with the embodiment 10, the prepared composite hydrogel has the embedding rate of 72.44 percent for NMN, can be formed into gel after being cooled at normal temperature after adding the curdlan, and has better gel forming effect and certain elasticity. In comparison with example 9, after the addition of carboxymethylcellulose, the gel has a strong water locking capacity, and after the preservation at a low temperature (5-10 ℃) in example 9, water oozes out after one day, and the water oozes out obviously after more than three days of preservation under the same conditions. The key effect of the curdlan on the gel forming property of the gel is shown, and the water locking property of the gel can be further improved by adding the sodium carboxymethyl cellulose.
Example 12
Step one, dissolving 0.05g of sodium carboxymethyl cellulose in 5mL of distilled water at normal temperature (20-25 ℃) to prepare sodium carboxymethyl cellulose solution with the mass fraction of 1.0%.
Dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the mass concentration of 0.1mol/L to obtain 2.7% of 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 microscopic views showing mixed solutions of examples 3, 11 and 12, respectively, and it can be seen from fig. 10 that the mixed sol of carboxymethyl cellulose and curdlan is uniformly dispersed before NMN is added, fig. 10 shows that particles of the mixed sol become larger after NMN is added in fig. 9, the structure is changed to a certain extent, and the particles are connected to form a certain sheet-like structure, and fig. 5 shows that the mixed sol after halloysite is added, and the particle structure of fig. 10 is more black than that of fig. 9. 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 NMN.
Example 13
Step one, 40mg halloysite was dissolved in 10mL distilled water to prepare a 2mg/mL solution.
Dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the mass concentration of 0.001mol/L to obtain 2.7% curdlan alkali solution, slowly dripping 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 with the temperature of 50 ℃ for heating and stirring.
Example 14
Step one, 40mg halloysite was dissolved in 10mL distilled water to prepare a 2mg/mL solution.
And step two, adding 20mgNMN into the solution in the step one, and stirring for 20min.
Step three, dissolving 0.8g of curdlan in 30mL of sodium hydroxide solution with the mass concentration of 0.001mol/L to obtain 2.7% curdlan alkali solution, slowly dripping 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 with the temperature of 50 ℃ for heating and stirring.
The composite hydrogel was tested for entrapment rate with an initial NMN mass of 20mg in the experiment. The resulting hydrogel had an entrapment rate of 88.90% for NMN.
Example 15
Step one, 20mg halloysite was dissolved in 10mL distilled water to prepare a 2mg/mL solution.
And step two, adding 20mgNMN into the solution obtained in the step two, and stirring for 30min.
As shown in fig. 11a and 11b, which are respectively a microscopic image of the halloysite solution obtained in the first step of example 15 and a microscopic image of the mixed solution obtained in the second step of example 15 after NMN is added, it can be seen that the pure halloysite solution in the first step of example 15 (fig. 11 a) is a dispersed hollow dot, and the mixed solution obtained in the second step of example 15 after NMN is added (fig. 11 b) has some agglomerated black lumps, which indicates that halloysite has adsorption, embedding and enrichment effects on NMN. Compared with the mixed solution of example 8 shown in fig. 6b, the embedding effect of example 8 on NMN is better, and the drug dispersion is more uniform after 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 medicine use process are avoided.
Claims (8)
1. An NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel, which is characterized in that: obtained by: firstly, adsorbing and loading NMN by utilizing a halloysite nano hollow tubular structure; then, adhering and wrapping the halloysite loaded with NMN by utilizing a three-dimensional network structure of sodium carboxymethyl cellulose molecules; finally, utilizing the torsion stretching effect of the curdlan in the process of gradually forming a triple helix hydrophobic structure at 50-85 ℃ to carry out torsion penetration with a three-dimensional network structure of sodium carboxymethyl cellulose so as to form a torsion interpenetrating network; the mass fraction of the curdlan is 1.11-2.67%, and the mass fraction of the sodium carboxymethylcellulose is 0.11-0.22%; the weight fraction of halloysite is 0.0022% -0.089%, and the weight fraction of NMN is 0.022% -0.089%.
2. The method for preparing the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel, as claimed in claim 1, is characterized in that: the method comprises the following steps: step one, dissolving sodium carboxymethyl cellulose in distilled water to obtain sodium carboxymethyl cellulose solution;
dissolving halloysite in distilled water to prepare a halloysite aqueous solution with the concentration of 0.1-2 mg/mL;
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 for adsorbing the NMN;
step four, dripping the halloysite aqueous solution for adsorbing NMN obtained in the step three into the sodium carboxymethyl cellulose solution prepared in the step one, and stirring to obtain mixed sol;
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 the curdlan alkali solution in a constant-temperature water bath with the temperature of 50-85 ℃, and stirring for a certain time to crosslink.
3. The preparation method according to claim 2, characterized in that: the acid-base property of all the solutions in the first to fourth steps is kept neutral.
4. The preparation method according to claim 2, characterized in that: 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 ℃.
5. The preparation method according to claim 2, characterized in that: in the second step, the mass concentration of 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 mg/mL-4 mg/mL, the stirring speed is 200-500 rpm, and the stirring is continued for 20-30 min.
6. The preparation method according to claim 2, characterized in that: in the fourth step, dropwise adding the halloysite aqueous solution for adsorbing NMN into the sodium carboxymethyl cellulose solution, wherein the dropwise adding speed is 30-60 drops/min; stirring is continuously carried out in the dripping process, and stirring is continuously carried out for 20-40 min after the dripping is finished, wherein the stirring speed in the whole process is 600-800 rpm.
7. The preparation method according to claim 2, characterized in that: in the fifth step, the mass concentration of the curdlan alkali solution is 0.0233 g/mL-0.0267 g/mL; continuously stirring the process of dissolving the curdlan 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 alkali solution is 0.0001 mol/L-0.1 mol/L; when the mixed sol is dripped into the curdlan alkali solution, the mixed sol is required to be dripped dropwise, the dripping time is controlled to be within 2-3 min, the stirring speed is 600-800 rpm in the whole process, and the temperature is controlled to be 50-60 ℃.
8. The application of the NMN-loaded halloysite/sodium carboxymethylcellulose/curdlan composite hydrogel in preparation of anti-aging drugs and/or health-care products with weight-losing functions as claimed in claim 1.
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