CN108926534A - KGM modified lecithin carries the transdermal alcohol plastid of NMN, preparation and its preparation process and application - Google Patents
KGM modified lecithin carries the transdermal alcohol plastid of NMN, preparation and its preparation process and application Download PDFInfo
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Abstract
The invention discloses a kind of KGM modified lecithins to carry the transdermal alcohol plastid of NMN, belong to pharmaceutical preparation production technical field, by percentage to the quality, it is grouped as by following group: NMN 0.03-1%, konjaku glucomannan 0.1-10%, phosphatidase 1-10%, cholesterol 0.05-1%, stabilizer 0.1-0.5%, antioxidant 0-1%, low-molecular-weight alcohol 5-50%, surplus are water.The KGM modified lecithin carries the transdermal alcohol plastid of NMN, it is a kind of novel form for spherical or subsphaeroidal multilamellar vesicles structure, with more stable thermodynamic behaviour, partial size is smaller, and encapsulation rate is high, have percutaneous abilities faster, it is stronger, skin-tolerant is good, dosage can be reduced, reduce the incidence of adverse reaction, improve safety.The preparation process of the gelling agent containing the alcohol plastid, alcohol plastid and gelling agent is also disclosed, its quality of the gelling agent is fine and smooth, and absorption of human body is good, and preparation process is simple, and mild condition is suitable for industrialized mass production.
Description
Technical field
The invention belongs to pharmaceutical preparation production technical fields, and it is modified to relate in particular to a kind of bioabsorbable polymer material KGM
Lecithin carries the transdermal alcohol plastid of NMN, preparation and its preparation process and application.
Background technique
Transdermal drug delivery system is a kind of novel Drug Delivery Systems, since it has the characteristics that more humane drug treatment and thoroughly
The continuous development of skin technology has become pharmaceutical industry one of field with fastest developing speed.It refers to is administered in skin surface, drug
Given pace penetrates skin layers, is entered Whole Body blood circulation by capillary and is reached effective blood drug concentration, realizes entirely
The novel form of body or local therapeutic effects.Compared to administration modes such as oral, intravenous injections, cutaneous penetration due to drug absorption not
It is influenced by the factors such as pH, food, transhipment time in alimentary canal, has avoidable liver and stomach and intestine first pass effect, reduction blood medicine dense
The fluctuation of degree, avoid drug to the stimulation of gastrointestinal tract, administration hurtless measure, compliance is strong the advantages that.
Barrier action due to keratoderma to Drug Percutaneous Absorption, so that most drugs, even some dosage
Drug low, curative effect is high, percutaneous rate and infiltration capacity are also difficult to meet the needs for the treatment of, are the weights for developing Percutaneously administrable preparation
Big obstacle.Alcohol plastid be it is a kind of with hypotoxicity, hypoimmunity, good cell compatibility substance, can load simultaneously water-soluble
Property, fat-soluble and macromolecular drug, have received widespread attention in drug delivery especially cutaneous penetration technical field.
The prominent feature of alcohol plastid is the ethyl alcohol containing higher volume fraction, so that imitated vesicle structure is made it have, form
Mostly subsphaeroidal or spherical, shape rounding is smooth, and the presence of ethyl alcohol improves lipophilicity and amphiphilic species in the phosphatide of vesica
The solubility of bilayer and aqueous center.In drug incorporation, liposome carries drug first and penetrates angle through intercellular pathways
Matter layer reaches deep skin, then discharges drug, is distributed drug to deep skin and drug percutaneous skin is promoted to absorb.
NMN (nicotinamide mononucleotide) can be converted to energy i (in vivo) and be metabolized essential " two nucleoside of nicotinamide adenine
Sour (NAD) " substance, the citrate cycle that can be used in glycolysis and cellular respiration.There are each living cells of human body by NMN
In, they react with oxygen, generate energy, and thousands of kinds of physiological metabolism reactions intracorporal to people all play vital work
With.How much closely bound up with many diseases the content of NMN is in human body cell, such as alzheimer's disease, Parkinson, muscular atrophy
Deng.In addition, the study found that cancer be because intracellular DNA by the attack of carcinogen after, by damage without and
Caused by Shi Xiufu, and NMN can activate DNA repair enzyme (PARP), repair the DNA of damage rapidly, it is prevented to evolve into cancer.
Moreover, NMN or superpower antioxidant, can remove interior free yl, prevent the process of cancer.
People can supplement NMN by diet for body, but the amount absorbed is very low, and NMN is highly unstable, easily
It degrades, NMN also has the characteristics that acid nonfast, cannot smoothly be absorbed after oral, pass through human body from the NMN of outside intake
When stomach, the influence that will receive gastric acid causes to lose activity, and absorptivity is generally relatively low, most of ingredient before reaching blood just
It is oxidized and degrades, keep its application limited.
NMN can also can be effectively prevented and decline with delaying skin by skin action pathway to external source is continuously replenished in body
The generation of old process.Showing NMN with prolonged application not only according to clinical verification has crease-resistant, nti-freckle to dispel outside the remarkable efficacies such as pigment, also
There is the effects of anti-inflammatory, sun-proof, health care, delay senescence.But since stability is poor at normal temperature, biological half-life is short, is easily digested
And have the shortcomings that immunogenicity, and limit its potential application.Currently, there are many administration mode, such as oral, injections by NMN
Deng, but due to the property of drug itself, inevitably result in the need for this disadvantage of frequent drug administration.In order to improve complying with for patient
Property, while increasing the bioavilability of NMN, and maintain constant effective blood drug concentration, exploitation can be spaced long period administration
NMN alcohol plastid has great meaning.
Summary of the invention
For this purpose, the present invention exactly will solve the problems, such as that above-mentioned NMN is difficult to effectively be administered, to propose that one kind can be by transdermal
The KGM modified lecithin of administration carries the transdermal alcohol plastid of NMN, preparation and its preparation process and application.
In order to solve the above technical problems, the technical solution of the present invention is as follows:
The present invention provides a kind of KGM modified lecithin and carries the transdermal alcohol plastid of NMN, the alcohol plastid by percentage to the quality,
It is grouped as by following group: NMN 0.03-1%, konjaku glucomannan 0.1-10%, phosphatidase 1-10%, cholesterol 0.05-1%, surely
Determine agent 0.1-0.5%, antioxidant 0-1%, low-molecular-weight alcohol 5-50%, surplus is water.
Preferably, the konjaku glucomannan includes quaternized konjaku glucomannan, it further include that carboxy methyl konjaku Portugal is sweet
At least one of glycan, oxidized konjac glucomannan, chitosan；The phosphatide is soybean lecithin, egg yolk lecithin, hydrogenation
At least one of soybean lecithin.
Preferably, the stabilizer is di(2-ethylhexyl)phosphate spermaceti rouge, phosphatide phthalein glycerol, phosphatidic acid, phosphatide phthalein serine and lotus
At least one of negative electricity phosphatide；The antioxidant is vitamin C, vitamin E, di-tert-butyl p-cresol, malic acid, β-Hu
At least one of radish element；The low-molecular-weight alcohol is the alcohol that carbon atom number is not more than 5.
The present invention also provides a kind of KGM modified lecithins to carry the transdermal ethosome gel of NMN, by the alcohol plastid with
Gelinite is mixed according to the volume ratio of 1:2-2:1, and the gelinite by percentage to the quality, is grouped as by following group: solidifying
Gel matrix 1-5%, moisturizer 2-15%, preservative 0.2-1%, permeation enhancers 0.3-10%, pH adjusting agent 1-5%, surplus are
Water.
Preferably, the gel-type vehicle is hypromellose, in carbomer, methylcellulose, sodium alginate
It is at least one；The moisturizer be dehydrated alcohol, glycerine, isopropanol, butanediol, hexylene glycol, sorbierite, polyethylene glycol, thoroughly
At least one of bright matter acid and Sodium Hyaluronate；The permeation enhancers are azone class, methyl sulfoxide class, organic alcohols, acetic acid
At least one of ethyl ester and mushroom alkenes.
Preferably, the preservative is in sorbic acid, potassium sorbate, benzyl alcohol, anesin, sodium benzoate
It is at least one or several；The pH adjusting agent is at least one of sodium hydroxide, potassium hydroxide, triethanolamine.
Preferably, the partial size of the alcohol plastid is 35-85 μm.
The present invention also provides a kind of methods for preparing the alcohol plastid comprising following steps:
S1, konjaku glucomannan, phosphatide, cholesterol, stabilizer and antioxidant are weighed in proportion, be uniformly mixed；
S2, it is proportionally added into low-molecular-weight alcohol, at 10-40 DEG C, the mixture for obtaining step S1 dissolves；
S3, it is proportionally added into NMN, after mixing, injects water；
S4, the solution for obtaining step S3 homogenization 2-20min under the revolving speed of 10-8000r/min；
S5, the solution after homogeneous is ultrasonically treated 2-45min, up to alcohol plastid solution after filtering.
The present invention also provides a kind of methods for preparing the gelling agent comprising the step of preparing alcohol plastid and preparation are solidifying
The step of colloid, wherein the preparation step of the alcohol plastid are as follows:
A, konjaku glucomannan, phosphatide, cholesterol, stabilizer and antioxidant are weighed in proportion, are uniformly mixed；
B, it is proportionally added into low-molecular-weight alcohol, at 10-40 DEG C, the mixture for obtaining step S1 dissolves；
C, it is proportionally added into N, after mixing, injects water；
D, the solution for obtaining step S3 homogenization 2-20min under the revolving speed of 10-8000r/min；
E, the solution after homogeneous is ultrasonically treated 2-45min, up to alcohol plastid solution after filtering；
The preparation step of the gelinite are as follows: moisturizer, preservative are added after being sufficiently swollen gel-type vehicle with water, promotees to seep
Saturating agent pH adjusting agent is added while stirring, mixture ph is adjusted to neutrality to get gelinite；
After alcohol plastid obtained is mixed with gelinite, develop uniformly to get gel preparation.
The present invention also provides the alcohol plastid described in one kind treatment alzheimer's disease, Parkinson, muscular dystrophy medicine
Application in object and anti-oxidant, anti-aging preparation.
The above technical solution of the present invention has the following advantages over the prior art:
(1) KGM modified lecithin of the present invention carries the transdermal alcohol plastid of NMN, the alcohol plastid by percentage to the quality,
It is grouped as by following group: NMN 0.03-1%, konjaku glucomannan 0.1-10%, phosphatidase 1-10%, cholesterol 0.05-1%, surely
Determine agent 0.1-0.5%, antioxidant 0-1%, low-molecular-weight alcohol 5-50%, surplus is water.The alcohol plastid improves the life of NMN
Object availability can maintain constant effective blood drug concentration, therefore can extend the time interval of administration, solve conventional administration mode
Middle NMN easily digested, biological half-life end, stability difference problem, the KGM modified lecithin carries the transdermal alcohol plastid of NMN, is
A kind of novel form is spherical or subsphaeroidal multilamellar vesicles structure, has more stable thermodynamic behaviour, and partial size is smaller, encapsulating
Rate is high, have percutaneous abilities faster, it is stronger, skin-tolerant is good, can reduce dosage, reduces the incidence of adverse reaction, mentions
High security.
(2) KGM modified lecithin of the present invention carries the transdermal ethosome gel of NMN, by the alcohol plastid with
Gelinite is mixed according to the volume ratio of 1:2-2:1, and the gelinite by percentage to the quality, is grouped as by following group: solidifying
Gel matrix 1-5%, moisturizer 2-15%, preservative 0.2-1%, permeation enhancers 0.3-10%, pH adjusting agent 1-5%, surplus are
Water.The gel preparation can be used as cutaneous penetration medicament, and quality is fine and smooth, and absorption of human body is good, and NMN ingredient of arranging in pairs or groups has and subtracts
It is the diseases such as slow alzheimer's disease, delay skin aging, anti-inflammatory sun-proof and other effects, have a wide range of application, security performance it is high.
(3) KGM modified lecithin of the present invention carries the preparation method of the transdermal alcohol plastid of NMN and its gelling agent, uses
Stirring, homogeneous, ultrasound can obtain the alcohol plastid containing NMN, and alcohol plastid is uniformly mixed with gelinite up to gelling agent, alcohol plastid
And the preparation process of gel preparation is simple, mild condition is suitable for industrialized mass production.
Detailed description of the invention
In order to make the content of the present invention more clearly understood, it below according to specific embodiments of the present invention and combines
Attached drawing, the present invention is described in further detail, wherein
Fig. 1 is alcohol plastid vesica histogram of particle size distribution described in the embodiment of the present invention；
Fig. 2 is alcohol plastid vesica grading curve figure described in the embodiment of the present invention；
Fig. 3 is alcohol plastid transmission electron microscope (TEM) image described in the embodiment of the present invention；
Fig. 4 is alcohol plastid vitro cumulative releasing trend figure described in the embodiment of the present invention；
Fig. 5 is alcohol plastid transdermal test in vitro rate release profiles described in the embodiment of the present invention.
Specific embodiment
Embodiment 1
The present embodiment provides a kind of KGM modified lecithins to carry the transdermal alcohol plastid of NMN, and the alcohol plastid is with mass percent
Meter, is grouped as: NMN 0.03%, konjaku glucomannan 0.1%, phosphatidase 1 %, cholesterol 0.05%, stabilizer by following group
0.1%, antioxidant 0.15%, low-molecular-weight alcohol 5%, surplus are water.Wherein, the konjaku glucomannan (KGM) include etc.
The quaternized konjaku glucomannan (QKGM) and Carboxymethyl Konjac Glucomannan (CKGM) of amount, the phosphatide are soybean lecithin,
The stabilizer is di(2-ethylhexyl)phosphate spermaceti rouge, and the antioxidant is vitamin C, and the low-molecular-weight alcohol is glycerine.
The KGM modified lecithin carry the transdermal ethosome gel of NMN can be used for treating alzheimer's disease, Parkinson,
Application in the drug of muscular dystrophy and anti-oxidant, anti-aging preparation.
The present embodiment also provides a kind of KGM modified lecithin and carries the transdermal ethosome gel of NMN, by above-mentioned alcohol plastid with
Gelinite is mixed according to the volume ratio of 1:2, wherein the gelinite is by percentage to the quality, composed of the following components: solidifying
Gel matrix 1%, moisturizer 2%, preservative 0.2%, permeation enhancers 0.3%, pH adjusting agent 1%, surplus are water, wherein gel
Matrix is hypromellose, and moisturizer is dehydrated alcohol, and preservative is sorbic acid, and permeation enhancers are azone, pH tune
Section agent is sodium hydroxide.
The present embodiment also provides a kind of preparation process of KGM modified lecithin load transdermal alcohol plastid of NMN comprising following step
It is rapid:
S1, konjaku glucomannan, phosphatide, cholesterol, stabilizer and antioxidant are weighed in proportion, be uniformly mixed.
S2, it is proportionally added into low-molecular-weight alcohol, at 10 DEG C, the mixture for obtaining step S1 dissolves.
S3, be proportionally added into NMN, after mixing, inject water, the injection rate of water be the additional amount of water 2-10%/
Min is 2%/min in the present embodiment.
S4, the obtained solution of step S3 is placed in high speed dispersion homogenizer progress whole grain, the homogeneous under the revolving speed of 10r/min
Handle 20min.
S5, the solution after homogeneous is ultrasonically treated 2min, then successively after 0.45 μm, 0.22 μm micropore filtering film filtering of mistake
Up to the uniform alcohol plastid solution of particle diameter distribution, contain alcohol plastid vesica in the alcohol plastid solution, the alcohol plastid vesica
Partial size is 35-85 μm.
The present embodiment also provides a kind of technique for preparing KGM modified lecithin and carrying the transdermal Ethosomal gel body of NMN comprising
The step of being prepared alcohol plastid by above-mentioned steps and prepared gelinite, the preparation step of the gelinite are as follows: by gel-type vehicle in room
It is sufficiently swollen under temperature with water, moisturizer, preservative, permeation enhancers is added thereto, pH adjusting agent is then added while stirring will
Mixture ph is adjusted to neutrality, and is sufficiently mixed uniformly up to colorless transparent gel body.By the alcohol plastid and gelinite press than
Example mixing, development uniformly, obtain fine and smooth faint yellow KGM modified lecithin and carry the transdermal ethosome gel of NMN.
In this implementation, the NMN is prepared using following technique:
Using niacinamide, ATP and xylose as raw material, in Nampt, ribose-phosphate pyrophosphokinase, core
Sugar -5- phosphoric acid isomerase, ribulose -3- phosphoric acid isomerase, Xylulokinase and xylose isomerase catalytic action under occur
Reaction is made nicotinamide mononucleotide (NMN).
Substrate solution is added into reaction kettle, the MgCl of the xylose of ATP, 30mM containing 30mM, 20mM2, 10mM KC1 with
And the Tris-HCl buffer of l00mM, adjust pH to 7.5-8.0.Then following catalysis enzyme: ribose-phosphate pyrophosphokinase is added
6g/L substrate solution, ribose-5-phosphate isomerase 10g/L substrate solution, ribulose -3- phosphoric acid isomerase 11g/L substrate solution,
Xylulokinase 10g/L substrate solution, xylose isomerase 10g/L substrate solution.It is reacted after mixing evenly, in reaction process
Lasting stirring (mixing speed 50rp m), control reaction temperature are 35 DEG C, and maintenance pH value is 7.5-8.0.
After above-mentioned reaction carries out 4h, reaction solution is isolated, and reaction solution is sent into another reaction kettle, then to reaction solution
The ZnCl of the middle niacinamide that 60mM is added, 30mM2, l00mM Tris-HCl buffer and Nampt
15g/L substrate solution, the reaction was continued after mixing evenly, persistently stirs (mixing speed 50rpm) in reaction process, control reaction temperature
Degree is 35 DEG C, and maintenances pH value is 7.5-8.0, then is reacted after 4h up to nicotinamide mononucleotide crude product solution (containing NMN12mM),
Using filter, purifying, it is dry after up to nicotinamide mononucleotide finished product.
Embodiment 2
The present embodiment provides a kind of KGM modified lecithins to carry the transdermal alcohol plastid of NMN, and the alcohol plastid is with mass percent
Meter, is grouped as: NMN1%, konjaku glucomannan 10%, phosphatidase 1 0%, cholesterol 1%, stabilizer 0.5%, antioxygen by following group
Agent 1%, low-molecular-weight alcohol 50%, surplus are water.Wherein, the konjaku glucomannan (KGM) includes quaternized Amorphophallus rivieri glucomannan
Glycan (QKGM) and chitosan (CS), the mass ratio of the two are 1:2, and the phosphatide is egg yolk lecithin, and the stabilizer is phosphorus
The mixture of rouge phthalein glycerol and phosphate, the mass ratio of the two are 1:1, and the antioxidant is vitamin E, di-t-butyl to first
The mixture of phenol, the mass ratio of the two are 1:2, and the low-molecular-weight alcohol is ethyl alcohol.
The KGM modified lecithin carry the transdermal ethosome gel of NMN can be used for treating alzheimer's disease, Parkinson,
Application in the drug of muscular dystrophy and anti-oxidant, anti-aging preparation.
The present embodiment also provides a kind of KGM modified lecithin and carries the transdermal ethosome gel of NMN, by above-mentioned alcohol plastid with
Gelinite is mixed according to the volume ratio of 1:1, wherein the gelinite is by percentage to the quality, composed of the following components: solidifying
Gel matrix 5%, moisturizer 15%, preservative 1%, permeation enhancers 10%, pH adjusting agent 5%, surplus are water, wherein gel base
Matter is the mixture of carbomer gel matrix and methylcellulose, and the mass ratio of the two is 1:2, and moisturizer is glycerine, isopropyl
The mixture of pure and mild hexylene glycol, three's volume ratio are 1:1:0.5, and preservative is the mixture of benzyl alcohol, anesin, the two
Volume ratio be 1:1, permeation enhancers are the mixture of dimethyl sulfoxide and ethyl alcohol, and the volume ratio of the two is 1:1, and pH adjusting agent is
Triethanolamine.
The present embodiment also provides a kind of preparation process of KGM modified lecithin load transdermal alcohol plastid of NMN comprising following step
It is rapid:
S1, konjaku glucomannan, phosphatide, cholesterol, stabilizer and antioxidant are weighed in proportion, be uniformly mixed.
S2, it is proportionally added into low-molecular-weight alcohol, at 40 DEG C, the mixture for obtaining step S1 dissolves.
S3, be proportionally added into NMN, after mixing, inject water, the injection rate of water be the additional amount of water 2-10%/
Min is 5%/min in the present embodiment.
S4, the obtained solution of step S3 is placed in high speed dispersion homogenizer progress whole grain, under the revolving speed of 8000r/min
Matter handles 2min.
S5, the solution after homogeneous is ultrasonically treated 45min, then successively crosses 0.45 μm, 0.22 μm of micropore filtering film filtering
Afterwards up to the uniform alcohol plastid solution of particle diameter distribution, alcohol plastid vesica, the alcohol plastid vesica are contained in the alcohol plastid solution
Partial size be 35-85 μm.
The present embodiment also provides a kind of technique for preparing KGM modified lecithin and carrying the transdermal Ethosomal gel body of NMN comprising
The step of being prepared alcohol plastid by above-mentioned steps and prepared gelinite, the preparation step of the gelinite are as follows: by gel-type vehicle in room
It is sufficiently swollen under temperature with water, moisturizer, preservative, permeation enhancers is added thereto, pH adjusting agent is then added while stirring will
Mixture ph is adjusted to neutrality, and is sufficiently mixed uniformly up to colorless transparent gel body.By the alcohol plastid and gelinite press than
Example mixing, development uniformly, obtain fine and smooth faint yellow KGM modified lecithin and carry the transdermal ethosome gel of NMN.
Embodiment 3
The present embodiment provides a kind of KGM modified lecithins to carry the transdermal alcohol plastid of NMN, and the alcohol plastid is with mass percent
Meter, be grouped as by following group: NMN 5%, konjaku glucomannan 5.5%, phosphatidase 6 %, cholesterol 0.5%, stabilizer 0.3%,
Antioxidant 0.45%, low-molecular-weight alcohol 30%, surplus are water.Wherein, the konjaku glucomannan (KGM) includes oxidation konjaku
The mass ratio of the mixture of Glucomannan (OKGM) and quaternized konjaku glucomannan (QKGM), the two is 1:2, and the phosphatide is
Hydrogenated soy phosphatidyl choline, the stabilizer are phosphatide phthalein serine, and the antioxidant is the mixing of malic acid, beta carotene
Object, the mass ratio of the two are 1:1, and the low-molecular-weight alcohol is the mixture of n-butanol and ethyl alcohol, and the two volume ratio is 1:2.
The KGM modified lecithin carry the transdermal ethosome gel of NMN can be used for treating alzheimer's disease, Parkinson,
Application in the drug of muscular dystrophy and anti-oxidant, anti-aging preparation.
The present embodiment also provides a kind of KGM modified lecithin and carries the transdermal ethosome gel of NMN, by above-mentioned alcohol plastid with
Gelinite is mixed according to the volume ratio of 2:1, wherein the gelinite is by percentage to the quality, composed of the following components: solidifying
Gel matrix 3%, moisturizer 9%, preservative 0.5%, permeation enhancers 6%, pH adjusting agent 3%, surplus are water, wherein gel base
Matter is the mixture of equivalent sodium alginate, methylcellulose, and moisturizer is the mixture of sorbierite, polyethylene glycol, hyaluronic acid,
Three's volume ratio is 1:1:2, and preservative is the mixture of benzyl alcohol, anesin, and the volume ratio of the two is 1:1, promotees infiltration
Agent is ethyl acetate, and pH adjusting agent is potassium hydroxide.
The present embodiment also provides a kind of preparation process of KGM modified lecithin load transdermal alcohol plastid of NMN comprising following step
It is rapid:
S1, konjaku glucomannan, phosphatide, cholesterol, stabilizer and antioxidant are weighed in proportion, be uniformly mixed.
S2, it is proportionally added into low-molecular-weight alcohol, at 25 DEG C, the mixture for obtaining step S1 dissolves.
S3, be proportionally added into NMN, after mixing, inject water, the injection rate of water be the additional amount of water 2-10%/
Min is 7%/min in the present embodiment.
S4, the obtained solution of step S3 is placed in high speed dispersion homogenizer progress whole grain, under the revolving speed of 500r/min
Matter handles 15min.
S5, the solution after homogeneous is ultrasonically treated 30min, then successively crosses 0.45 μm, 0.22 μm of micropore filtering film filtering
Afterwards up to the uniform alcohol plastid solution of particle diameter distribution, alcohol plastid vesica, the alcohol plastid vesica are contained in the alcohol plastid solution
Partial size be 35-85 μm.
The present embodiment also provides a kind of technique for preparing KGM modified lecithin and carrying the transdermal Ethosomal gel body of NMN comprising
The step of being prepared alcohol plastid by above-mentioned steps and prepared gelinite, the preparation step of the gelinite are as follows: by gel-type vehicle in room
It is sufficiently swollen under temperature with water, moisturizer, preservative, permeation enhancers is added thereto, pH adjusting agent is then added while stirring will
Mixture ph is adjusted to neutrality, and is sufficiently mixed uniformly up to colorless transparent gel body.By the alcohol plastid and gelinite press than
Example mixing, development uniformly, obtain fine and smooth faint yellow KGM modified lecithin and carry the transdermal ethosome gel of NMN.
Experimental example
1, KGM modified lecithin obtained by the test present invention carries the particle diameter distribution situation of the transdermal alcohol plastid vesica of NMN, knot
Fruit is as shown in Figure 1, average grain diameter is 57.2 μm.
2, KGM modified lecithin obtained by the test present invention carries the particle diameter distribution situation of the transdermal alcohol plastid vesica of NMN, knot
Fruit as shown in Fig. 2, most of vesica particle diameter distribution at 35-85 μm.
3, the images of transmissive electron microscope that KGM modified lecithin of the present invention carries the transdermal alcohol plastid of NMN is tested, as a result as schemed
Shown in 3, test result shows that the alcohol plastid exists in the form of the vesica to differ in size.
4, rat transdermal experiment tests KGM modified lecithin of the present invention and carries the saturating of the transdermal ethosome gel of NMN
Skin release rate, test results are shown in figure 4, test result show the accumulative release rate of the alcohol plastid for 24 hours up to 30%, surely
State percutaneous rate is 1331.24 μ g/cm2, illustrate it with certain controlled-release function.
5, the dermal penetration rate release profiles that KGM modified lecithin of the present invention carries the transdermal alcohol plastid of NMN are tested,
As a result as shown in figure 5, test result shows that the alcohol plastid meets transdermal kinetic theory, penetration kinetics equation are as follows: Q=
59.34t-20.91, wherein steady-state permeation rate is Js=59.34 μ gxh-1·cm-2。
It is not stratified, do not precipitate in addition, standing experiment shows 120 days solution remained stables of the alcohol plastid solution left standstill.
Obviously, the above embodiments are merely examples for clarifying the description, and does not limit the embodiments.It is right
For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of variation or
It changes.There is no necessity and possibility to exhaust all the enbodiments.And it is extended from this it is obvious variation or
It changes still within the protection scope of the invention.
Claims (10)
1. a kind of KGM modified lecithin carries the transdermal alcohol plastid of NMN, which is characterized in that the alcohol plastid by percentage to the quality, by
Following group is grouped as: NMN 0.03-1%, konjaku glucomannan 0.1-10%, phosphatidase 1-10%, cholesterol 0.05-1% stablize
Agent 0.1-0.5%, antioxidant 0-1%, low-molecular-weight alcohol 5-50%, surplus are water.
2. KGM modified lecithin according to claim 1 carries the transdermal alcohol plastid of NMN, which is characterized in that the Amorphophallus rivieri glucomannan
Glycan includes quaternized konjaku glucomannan, further includes Carboxymethyl Konjac Glucomannan, oxidized konjac glucomannan, in chitosan
At least one；The phosphatide is at least one of soybean lecithin, egg yolk lecithin, hydrogenated soy phosphatidyl choline.
3. KGM modified lecithin according to claim 2 carries the transdermal alcohol plastid of NMN, which is characterized in that the stabilizer is
At least one of di(2-ethylhexyl)phosphate spermaceti rouge, phosphatide phthalein glycerol, phosphatidic acid, phosphatide phthalein serine and bear electricity phosphatide；The antioxygen
Agent is at least one of vitamin C, vitamin E, di-tert-butyl p-cresol, malic acid, beta carotene；The low molecule
Measuring alcohol is the alcohol that carbon atom number is not more than 5.
4. a kind of KGM modified lecithin carries the transdermal ethosome gel of NMN, which is characterized in that by any one of such as claim 1-3
The alcohol plastid and gelinite is mixed according to the volume ratio of 1:2-2:1, the gelinite by percentage to the quality, by such as
The following group is grouped as: gel-type vehicle 1-5%, moisturizer 2-15%, preservative 0.2-1%, permeation enhancers 0.3-10%, pH adjusting agent
1-5%, surplus are water.
5. KGM modified lecithin according to claim 4 carries the transdermal ethosome gel of NMN, which is characterized in that described solidifying
Gel matrix is at least one of hypromellose, carbomer, methylcellulose, sodium alginate；The moisturizer is nothing
In water-ethanol, glycerine, isopropanol, butanediol, hexylene glycol, sorbierite, polyethylene glycol, hyaluronic acid and Sodium Hyaluronate extremely
Few one kind；The permeation enhancers are at least one in azone class, methyl sulfoxide class, organic alcohols, ethyl acetate and mushroom alkenes
Kind.
6. KGM modified lecithin according to claim 5 carries the transdermal ethosome gel of NMN, which is characterized in that described anti-
Rotten agent is selected from least one of sorbic acid, potassium sorbate, benzyl alcohol, anesin, sodium benzoate or several；The pH tune
Section agent is at least one of sodium hydroxide, potassium hydroxide, triethanolamine.
7. KGM modified lecithin according to claim 6 carries the transdermal ethosome gel of NMN, which is characterized in that the alcohol
The partial size of plastid is 35-85 μm.
8. a kind of method for preparing alcohol plastid as described in any one of claims 1-3, which comprises the steps of:
S1, konjaku glucomannan, phosphatide, cholesterol, stabilizer and antioxidant are weighed in proportion, be uniformly mixed；
S2, it is proportionally added into low-molecular-weight alcohol, at 10-40 DEG C, the mixture for obtaining step S1 dissolves；
S3, it is proportionally added into NMN, after mixing, injects water；
S4, the solution for obtaining step S3 homogenization 2-20min under the revolving speed of 10-8000r/min；
S5, the solution after homogeneous is ultrasonically treated 2-45min, up to alcohol plastid solution after filtering.
9. a kind of prepare the method such as the described in any item gelling agents of claim 4-6, which is characterized in that including preparing alcohol plastid
The step of and the step of prepare gelinite, wherein the preparation step of the alcohol plastid are as follows:
A, konjaku glucomannan, phosphatide, cholesterol, stabilizer and antioxidant are weighed in proportion, are uniformly mixed；
B, it is proportionally added into low-molecular-weight alcohol, at 10-40 DEG C, the mixture for obtaining step S1 dissolves；
C, it is proportionally added into NMN, after mixing, injects water；
D, the solution for obtaining step S3 homogenization 2-20min under the revolving speed of 10-8000r/min；
E, the solution after homogeneous is ultrasonically treated 2-45min, up to alcohol plastid solution after filtering；
The preparation step of the gelinite are as follows: moisturizer, preservative, permeation enhancers are added after being sufficiently swollen gel-type vehicle with water
PH adjusting agent is added while stirring mixture ph is adjusted to neutrality to get gelinite；
After alcohol plastid obtained is mixed with gelinite, develop uniformly to get gel preparation.
10. a kind of alcohol plastid as described in any one of claims 1-3 is in treatment alzheimer's disease, Parkinson, muscular atrophy
Application in the drug of disease and anti-oxidant, anti-aging preparation.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111166760A (en) * | 2019-12-17 | 2020-05-19 | 浙江安赛新材料科技有限公司 | composition of beta-nicotinamide mononucleotide or precursor thereof, preparation method and application |
| CN112618515A (en) * | 2020-12-29 | 2021-04-09 | 江南大学 | Preparation method of exosome-loaded oral colon-targeted drug delivery polymer |
| CN113456527A (en) * | 2021-07-30 | 2021-10-01 | 北京清大赛尔生物科技有限公司 | NADH microcapsule preparation and preparation method and application thereof |
| CN114129509A (en) * | 2021-12-03 | 2022-03-04 | 药酚享科技(北京)有限公司 | Moisturizing NMN hydrophilic gel and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552147A (en) * | 2011-02-11 | 2012-07-11 | 舒泰神（北京）生物制药股份有限公司 | Bullatacin ethosome gel and preparation method thereof |
| CN108186572A (en) * | 2018-02-11 | 2018-06-22 | 湖北工业大学 | The konjaku glucomannan of injection tool pH sensibility-liposome composite Nano pharmaceutical carrier and its preparation and application |
-
2018
- 2018-08-27 CN CN201810979314.9A patent/CN108926534B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102552147A (en) * | 2011-02-11 | 2012-07-11 | 舒泰神（北京）生物制药股份有限公司 | Bullatacin ethosome gel and preparation method thereof |
| CN108186572A (en) * | 2018-02-11 | 2018-06-22 | 湖北工业大学 | The konjaku glucomannan of injection tool pH sensibility-liposome composite Nano pharmaceutical carrier and its preparation and application |
Non-Patent Citations (1)
| Title |
|---|
| 赵娟等: "烟酰胺单核苷酸的研究及应用进展", 《食品科技》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111166760A (en) * | 2019-12-17 | 2020-05-19 | 浙江安赛新材料科技有限公司 | composition of beta-nicotinamide mononucleotide or precursor thereof, preparation method and application |
| CN112618515A (en) * | 2020-12-29 | 2021-04-09 | 江南大学 | Preparation method of exosome-loaded oral colon-targeted drug delivery polymer |
| CN112618515B (en) * | 2020-12-29 | 2021-09-24 | 江南大学 | Preparation method of exosome-loaded oral colon-targeted drug delivery polymer |
| CN113456527A (en) * | 2021-07-30 | 2021-10-01 | 北京清大赛尔生物科技有限公司 | NADH microcapsule preparation and preparation method and application thereof |
| CN113456527B (en) * | 2021-07-30 | 2023-04-07 | 北京清大赛尔生物科技有限公司 | NADH microcapsule preparation and preparation method and application thereof |
| CN114129509A (en) * | 2021-12-03 | 2022-03-04 | 药酚享科技(北京)有限公司 | Moisturizing NMN hydrophilic gel and preparation method thereof |
| CN114129509B (en) * | 2021-12-03 | 2023-12-01 | 药酚享科技(北京)有限公司 | Moisturizing NMN hydrophilic gel and preparation method thereof |
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