CN109908089A - Nanosphere and the preparation method and application thereof containing NADH or NADPH - Google Patents
Nanosphere and the preparation method and application thereof containing NADH or NADPH Download PDFInfo
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- CN109908089A CN109908089A CN201910237240.6A CN201910237240A CN109908089A CN 109908089 A CN109908089 A CN 109908089A CN 201910237240 A CN201910237240 A CN 201910237240A CN 109908089 A CN109908089 A CN 109908089A
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- nadh
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The invention discloses a kind of nanospheres containing NADH or NADPH, in parts by weight, the nanosphere includes 30~70 parts of pharmaceutically available macromolecule carrier, NADH or NADPH and 0~15 of 20~50 parts part of adhesive, and the NADH or NADPH are at least partly scattered in the inside of the macromolecule carrier.The invention also discloses the preparation methods of the nanosphere containing NADH or NADPH described in one kind.The invention also discloses a kind of pharmaceutical preparations, include the nanosphere containing NADH or NADPH and pharmaceutically acceptable auxiliary material.The invention also discloses application of the nanosphere containing NADH or NADPH described in one kind in treatment disease.
Description
Technical field
The present invention relates to medicine and health product technology field more particularly to a kind of nanosphere containing NADH or NADPH and
Preparation method and application.
Background technique
Icotinamide-adenine dinucleo (NADH) and nicotinamide-adenine-phosphoric acid-dinucleotides (NADPH) are human bodies
Interior physiologically substance is present in all living cells including human cell.These substances are the confactors of many enzymes,
And these enzymes major part all can catalytic oxidization-reduction reaction.
Thousands of kinds of physiological metabolism reactions in NADH or NADPH participant's body in gene repair, improve immunity, anti-oxidant
And improve sleep etc. play an important role, sufficient NADH or NADPH can allow body preferably to be protected, prevention with
And control disease, and then guarantee health.So supplement NADH or NADPH may advantageously facilitate the various physiological functions of body in vitro
Keep optimum state.However NADH or NADPH are the hydrogen of biological form, oxygen, moisture in illumination, acidic environment or air
The molecular structure that NADH or NADPH will be destroyed causes its chemical property extremely unstable (needing instant match).Further, since
The acid nonfast feature of NADH or NADPH, so that meeting loss of activity is influenced by gastric acid from the NADH or NADPH of outside intake,
So as to cause can not take orally.
Summary of the invention
In view of this, the present invention provides, a kind of stability is good, the easy to maintain and orally available nanometer containing NADH or NADPH
Microballoon.
In addition, there is a need to provide the preparation method of the nanosphere containing NADH or NADPH described in one kind.
In addition, there is a need to provide the pharmaceutical preparation of the nanosphere containing NADH or NADPH described in one kind and above-mentioned contain
The application of the nanosphere of NADH or NADPH.
The present invention provides a kind of nanosphere containing NADH or NADPH, and in parts by weight, which includes 30~70
The pharmaceutically available macromolecule carrier, NADH or NADPH and 0~15 of 20~50 parts part of adhesive of part, the NADH
Or NADPH is at least partly scattered in the inside of the macromolecule carrier.
The present invention also provides the preparation methods of the nanosphere containing NADH or NADPH described in one kind, include the following steps:
In parts by weight, 30~70 parts of pharmaceutically available macromolecule carrier and solvent are mixed to get colloidal sol or emulsification
Liquid；
It heats the colloidal sol or the emulsion and obtains macromolecule carrier solution after filtering；
In parts by weight, 20~50 parts of NADH or NADPH are added in the macromolecule carrier solution, and are added 0
A mixed liquor is obtained after~15 parts of adhesive mixing；And
Cooling, solidification and the dry mixed liquor, to obtain the nanosphere containing NADH or NADPH.
The present invention also provides a kind of pharmaceutical preparations, can comprising the nanosphere containing NADH or NADPH and pharmaceutically connect
The auxiliary material received.
The present invention also provides the nanospheres containing NADH or NADPH described in one kind in treatment the nervous system disease, heart and brain
Application in vascular system disease.
Advantage for present invention: the nanosphere containing NADH or NADPH provided by the invention make NADH or
NADPH is effectively protected, solve the problems, such as it is labile after it meets light or oxygen, extend NADH or NADPH effectively at
Point holding time, reduce preservation difficulty.
Detailed description of the invention
Fig. 1 is the preparation flow figure of the nanosphere containing NADH or NADPH in present pre-ferred embodiments.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
Unless otherwise defined, all technical and scientific terms used herein and belong to technical field of the invention
The normally understood meaning of technical staff is identical.Term as used herein in the specification of the present invention is intended merely to description tool
The purpose of the embodiment of body, it is not intended that in the limitation present invention.
Better embodiment of the present invention provides a kind of nanosphere containing NADH or NADPH, in parts by weight, including 30~
70 parts of pharmaceutically available macromolecule carrier, NADH or NADPH and 0~15 of 20~50 parts part of adhesive, it is described
NADH or NADPH is at least partly scattered in the inside of the macromolecule carrier.
The macromolecule carrier is in three-dimensional net structure, and the macromolecule carrier includes gelatin, Arabic gum, alginic acid
At least one of salt, chitosan, starch, polysaccharide, cyclodextrin, fibroin and albumin.Described adhesive includes Guar
At least one of glue, xanthan gum and locust bean gum.
In the present embodiment, in parts by weight, the nanosphere containing NADH or NADPH further includes 0~15 part
Stabilizer, the stabilizer include at least one of vitamin E, chlorophyll, reproducibility ferredoxin and vitamin C.
The partial size of the nanosphere containing NADH or NADPH is 10~200nm.
Referring to Fig. 1, better embodiment of the present invention also provides the nanosphere containing NADH or NADPH described in a kind of prepare
Method, include the following steps:
30~70 parts of macromolecule carrier and solvent are mixed to get colloidal sol or emulsion by S11, in parts by weight.
In the present embodiment, 5~100 parts of solvent is added in Xiang Suoshu macromolecule carrier makes it be swollen 10~20h, system
At colloidal sol or emulsion.The solvent includes in the acetum that water, vegetable oil (soybean oil) and concentration are 2%~10%
It is at least one.Preferably, the solvent is water.Wherein, the weight ratio of the macromolecule carrier and water is 1:5~10.
S12, the colloidal sol or the emulsion are heated and obtains macromolecule carrier solution after filtering.
In the present embodiment, the colloidal sol or the emulsion heat 15~35min at 40~60 DEG C.If described
The temperature of heating is too low, and the macromolecule carrier can solidify；If the temperature of the heating is excessively high, the macromolecule carrier can drop
Solution.
S13, in parts by weight, 20~50 parts of NADH or NADPH are added in the macromolecule carrier solution, and are added
A mixed liquor is obtained after entering 0~15 part of adhesive mixing.
In the present embodiment, after the NADH or NADPH is added, 20min is stirred with the revolving speed of 1000-1500r/min
Uniformly mixed mixed liquor is obtained afterwards.Wherein, the weight ratio of NADH or NADPH and the macromolecule carrier is 1:1~4.
Preferably, in parts by weight, 0~5 part of stabilizer can also be added in the whipping process.Described adhesive packet
Include the one of which in guar gum, xanthan gum and locust bean gum.The stabilizer includes vitamin E, chlorophyll, reproducibility iron oxygen
One of which also in albumen and vitamin C.
S14, cooling, solidification and the dry mixed liquor, to obtain the nanosphere containing NADH or NADPH.
In the present embodiment, the mixed liquor is placed in ice-water bath and is cooled to 0~10 DEG C.The temperature of the drying
Not higher than 50 degree, avoid the macromolecule carrier that degradation and the nanosphere balling-up effect containing NADH or NADPH occurs
It is bad, and the molecular structure of NADH or NADPH is avoided to destroy.
Preferably, the pH to 6~8 that sodium hydroxide adjusts the mixed liquor can also be added in the solidification process, with
Accelerate the solidification of the mixed liquor.In addition, the pH to 6~8 for adjusting the mixed liquor also may make NADH or NADPH more steady
It is fixed, on the fiber for easily adhering to the macromolecule carrier.
Preferably, the food additive that concentration is 1%~10% can also be added in the mixed liquor and add curing agent to be consolidated
Change, then use water or brine, the nanosphere containing NADH or NADPH is obtained after being finally dried in vacuo.It is described
Food additive adds curing agent that can be calcium chloride, calcium gluconate, calcium monohydrogen phosphate or calcium dihydrogen phosphate.
Preferably, the nanosphere containing NADH or NADPH can pass through 20 mesh or 25 mesh sieves.
The present invention also provides a kind of pharmaceutical preparations, can comprising the nanosphere containing NADH or NADPH and pharmaceutically connect
The auxiliary material received.
The pharmaceutical preparation be tablet, pulvis, capsule, granule, pill, suspension, solution, syrup, mixture,
One of which in powder, medicinal powder and dripping pill.
Preferably, the tablet include in conventional tablet, coated tablet, film coating tablet and enteric coated tablet wherein
It is a kind of.
In the present embodiment, the conventional tablet refers to is not wrapped by what compression after directly compressing or granulating obtained
Garment piece agent.
In the present embodiment, the coated tablet refers to the tablet for being enclosed with acid stable coating.Wherein, the acidity
Stablizing coating includes cellulose acetate, phthalic acid ester, polyvinylacetate phthalate, hydrox-propyl-methyl
One of which in cellulose, phthalic acid ester, methacrylic acid copolymer, rouge-wax, shellac and zein.
In the present embodiment, the film coating tablet is the aqueous paint (water-based varnishes) of covering
Coated tablet.Wherein, the aqueous paint can have the function of enteric.Preferably, the aqueous paint is selected from lac (lac
TM) or its salt, methacrylate, cellulose acetophthalates (acetyl phthalate cellulose), titanium dioxide, talcum,
Triethyl citrate, PVP K30, curcumin, lutein, hydroxypropylcellulose, hydroxypropyl methyl cellulose or their mixture.
In the present embodiment, the enteric coated tablet is referred to unchanged through gastric barrier (gastric
Barrier tablet).
The pharmaceutically acceptable auxiliary material include mannitol, microcrystalline cellulose, magnesium stearate, carboxymethyl cellulose and
One of which in calcium monohydrogen phosphate.
The suitable oral single dose of NADH or NADPH is 5~500mg.Preferably, NADH's or NADPH is suitable oral
Single dose is 5~200mg.The dosage for oral use of suitable day of NADH or NADPH is 5~1500mg.Preferably, NADH or
The dosage for oral use of suitable day of NADPH is 5~200mg.
The present invention also provides application of the nanosphere containing NADH or NADPH described in one kind in treatment disease.In this reality
It applies in mode, the nanosphere containing NADH or NADPH can be used for treating the nervous system disease, diseases of cardiovascular and cerebrovascular systems.
The nanosphere containing NADH or NADPH can also be used to treat parkinsonism, Alzheimer's disease, phenylketonuria, depression
The diseases such as disease, obesity, diabetes and cancer.
The present invention is specifically described below by embodiment.
Embodiment 1
The preparation of nanosphere containing NADH:
(1), the gelatin in parts by weight, weighing 30 parts, 50 parts of distilled water is added into gelatin is made its swelling 10h
The colloidal sol is heated 35min at 40 DEG C, gelatin solution is obtained by filtration by colloidal sol.
(2), in parts by weight, 20 parts of NADH is added in institute's gelatine solution, is stirred with the revolving speed of 1000r/min
20min, and 15 parts of adhesive of addition and 15 parts of stabilizer, described adhesive are xanthan gum, the stabilizer in stirring
For vitamin E, a mixed liquor is obtained.
(3), the mixed liquor is placed in ice-water bath and is cooled to 0~10 DEG C, sodium hydroxide is added and adjusts the mixing
The pH of liquid is 6~8, and solidification obtains the nanosphere containing NADH after vacuum drying.
Embodiment 2
The preparation of nanosphere containing NADPH:
(1), the Arabic gum in parts by weight, weighing 40 parts, 50 parts of distilled water is added into Arabic gum keeps its molten
Colloidal sol is made in swollen 10~20h, and the colloidal sol is heated 25min at 50 DEG C, gumwater is obtained by filtration.
(2), in parts by weight, 20 parts of NADPH is added in the gumwater, with turning for 1500r/min
Speed stirring 20min, and 10 parts of adhesive and 15 parts of stabilizer are added in stirring, described adhesive is guar gum, described
Stabilizer is chlorophyll, obtains a mixed liquor.
(3), the mixed liquor is placed in ice-water bath and is cooled to 0~10 DEG C, instilling concentration in Xiang Suoshu mixed liquor is
1%~10% calcium chloride solution is solidified, and is washed with sodium chloride solution, and obtains the nanometer containing NADPH after being dried in vacuo
The nanosphere containing NADPH is crossed 20 mesh or 25 mesh sieves by microballoon.
Embodiment 3
The preparation of nanosphere containing NADH:
(1), the chitosan in parts by weight, weighing 50 parts, 100 parts of distilled water is added into chitosan makes it be swollen 10
Colloidal sol is made in~20h, and the colloidal sol is heated 15min at 60 DEG C, chitosan solution is obtained by filtration.
(2), in parts by weight, 20 parts of NADH is added in the chitosan solution, is stirred with the revolving speed of 1200r/min
20min is mixed, and 5 parts of adhesive of addition and 15 parts of stabilizer, described adhesive are guar gum, the stabilization in stirring
Agent is chlorophyll, obtains a mixed liquor.
(3), the mixed liquor is placed in ice-water bath and is cooled to 0~10 DEG C, solidification is obtained after vacuum drying containing NADH
Nanosphere, into the nanosphere containing NADH be added concentration be 70% ethyl alcohol, will weigh described in weight and contained
The nanosphere of NADH is placed on a set of sieve that screen size is successively decreased from inside to outside, the nanosphere containing NADH according to
Grain size stays in each layer compass screen surface respectively, obtains particle wet feed, the particle wet feed is dried in vacuo to 0.5 at 10~50 DEG C~
Obtain the nanosphere containing NADH of uniform particle sizes afterwards for 24 hours.
Embodiment 4
Carry out the preparation of tablets and capsules respectively using the nanosphere made from embodiment 1 containing NADH:
The preparation of tablet:
(1), it weighs: weighing the nanosphere containing NADH, the PEARLITOL 25C of 40g and the microcrystalline cellulose of 20g of 10g.
(2), it mixes tabletting: adding the magnesium stearate of 0.5g in step (1), mix, tabletting, obtain producing among one
Object.
(3), it is coated: with the intermediate product in the isolation coat of 2.5g and the enteric coating liquid encapsulation steps (2) of 8g.
(4), tablet is made.
The preparation of capsule:
(1), it weighs: weighing the nanosphere containing NADH, the PEARLITOL 25C of 40g and the microcrystalline cellulose of 30g of 10g.
(2), it mixes: adding the polyvinylpyrrolidone of 10g, the magnesium stearate of 6g and the pre- glue of 4g in step (1)
Change starch, mixes, obtain a mixture.
(3), the mixture in step (2) is packed by commercially available edibility hard or soft capsule shell by the method for quantitative filling
In to get arrive capsule preparations.
Tablet made from embodiment 4 is impregnated into 2h under conditions of simulation hydrochloric acid solution S GF pH=2, is then tied in simulation
6h is impregnated under conditions of enteric liquid SCF pH=6.8, tests the release rate of 2h, 4h, 6h and 8h NADH, test knot respectively
Fruit is as shown in table 1.
The nanosphere containing NADH in 1 embodiment 4 of table is made after tablet in simulation hydrochloric acid solution and simulation colon solution
The release rate of effective component after immersion
| Time h | Release rate % |
| 0 | 0 |
| 2 | 1.35 |
| 4 | 22.78 |
| 6 | 63.54 |
| 8 | 95.46 |
| Surplus | 0.10 |
| Total amount | 95.68 |
Tablet made from embodiment 4 is impregnated into 8h under conditions of simulating colon solution S CF pH=6.8, tests respectively
The release rate of 2h, 4h, 6h and 8h NADH, test result are as shown in table 2.
The effective component after simulation colon solution impregnates is made after tablet in the nanosphere containing NADH in 2 embodiment 4 of table
Release rate
Above-mentioned test result show simulation hydrochloric acid solution and simulation colon solution impregnate under, tablet made from embodiment 4
Middle effective component NADH can be sustained into solution, be a kind of long-acting medicament.
Tablet made from embodiment 4 is placed in 100 DEG C of baking ovens and heats 1h, 2h, 3h, 4h and 5h respectively, is then weighed
The reduction quality of sample, test result are as shown in table 3.
The nanosphere containing NADH in 3 embodiment 4 of table is made after tablet heat in an oven after sample quality reduction
Amount
| Time h | Mass lost % |
| 0 | 0 |
| 1 | 0.053 |
| 2 | 0.031 |
| 3 | 0.018 |
| 4 | 0.015 |
| 5 | 0.06 |
From table 3 it is observed that preceding 3h sample quality reduction is more, main cause is the volatilization of moisture, continues to heat 5h
Afterwards, the Mass lost of sample is almost nil, illustrates that the stability of sample is preferable.
The above technical solution of the present invention has the following advantages over the prior art:
(1) the available macromolecule carrier of pharmacy is generally the linear polymeric of a variety of amino acid compositions, is used as base
Body material, embeds NADH or NADPH in the form of being crosslinked inierpeneirating network structure, microballoon, to make NADH or NADPH
Protected, solve the problems, such as it is labile after it meets light or oxygen, when extending the preservation of NADH or NADPH effective component
Between, reduce preservation difficulty.
(2) in the nanosphere containing NADH or NADPH of the invention, most of NADH or NADPH are scattered in described
The inside of the crosslinking interpenetrating networks of macromolecule carrier, small part are carried on the macromolecule carrier outer surface.This three-dimensional interpenetrating
The macromolecule carrier of network structure has both bioactivity and loads the effect of NADH or NADPH effective component, makes to be carried on
NADH or NADPH between network structure are protected, and are solved NADH or NADPH and are met gastric acid fast decoupled, are unable to give full play
The problem of effectiveness is a kind of macromolecule carrier with intestinal sustained releasing effect, is that NADH or NADPH treats parkinsonism, A Er
The diseases such as Ci Haimo disease, depression and cancer provide a kind of ideal pharmaceutical carrier.It has by being sustained NADH or NADPH
Ingredient is imitated, activation DNA repair enzyme repairs DNA, further the generation of acceptable pre- anti-cancer.
(3) macromolecule carrier is a kind of natural macromolecule soluble dietary fiber, and viscosity is high, water suction is more, swollen
It is swollen fast, there is good biological functionality and compatibility, safety and microbic resolvability.For example, gelatin had not only contained carboxyl but also had contained
Amino is a kind of ampholytes, and NADH or NADPH both ampholytes containing amino containing hydroxyl, so that the height
It can be good at reaching stable state by electrolytic equilibrium between molecular vehicle and the NADH or NADPH.
(4) heretofore described adhesive has good adhesive effect, can be effectively by the fibre of the macromolecule carrier
Dimension is bonded together, and is easier to it agglomerating, while can also form layer protecting film on the surface NADH, protects it from by gastric acid point
Solution, and it is made to be sustained out.In addition, the stability of NADH can be enhanced in the stabilizer of the invention, vitamin E has relatively strong
Inoxidizability, chlorophyll also can effectively prevent the oxygenolysis of NADH.
(5) preparation process of the invention is easy to operate, and preparation is convenient, industrial applicibility with higher.By condensation or
Vacuum drying mode forms, easy to operate, it is good to be made into nanosphere form, and partial size is small, easily absorbs.
(6) nanosphere of the present invention containing NADH or NADPH can also be further prepared into tablet, capsule,
The peroral dosage forms such as granula, pill, suspension, solution, syrup, mixture, powder, medicinal powder, dripping pill are answered for NADH or NADPH
It is used to prepare the drug for the treatment of disease, provides more dosage form selections.
The above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although referring to preferred embodiment to this hair
It is bright to be described in detail, those skilled in the art should understand that, technical solution of the present invention can be repaired
Change or equivalent replacement, without departing from the spirit of the technical scheme of the invention and essence.
Claims (11)
1. a kind of nanosphere containing NADH or NADPH, which is characterized in that in parts by weight, which includes 30~70
The pharmaceutically available macromolecule carrier, NADH or NADPH and 0~15 of 20~50 parts part of adhesive of part, the NADH
Or NADPH is at least partly scattered in the inside of the macromolecule carrier.
2. the nanosphere as described in claim 1 containing NADH or NADPH, which is characterized in that described containing NADH's or NADPH
The partial size of nanosphere is 10~200nm.
3. the nanosphere as described in claim 1 containing NADH or NADPH, which is characterized in that the macromolecule carrier is in three
Tie up network structure, the macromolecule carrier include gelatin, Arabic gum, alginate, chitosan, starch, polysaccharide, cyclodextrin,
At least one of fibroin and albumin, described adhesive include in guar gum, xanthan gum and locust bean gum at least
It is a kind of.
4. the nanosphere as described in claim 1 containing NADH or NADPH, which is characterized in that in parts by weight, described to contain
The nanosphere of NADH or NADPH further includes 0~15 part of stabilizer, and the stabilizer includes vitamin E, chlorophyll, reduction
Property at least one of ferredoxin and vitamin C.
5. a kind of preparation method of the nanosphere according to any one of claims 1-4 containing NADH or NADPH, feature exist
In including the following steps:
In parts by weight, 30~70 parts of pharmaceutically available macromolecule carrier and solvent are mixed to get colloidal sol or emulsion；
It heats the colloidal sol or the emulsion and obtains macromolecule carrier solution after filtering；
In parts by weight, 20~50 parts of NADH or NADPH are added in the macromolecule carrier solution, and are added 0~15
A mixed liquor is obtained after the adhesive mixing of part；And
Cooling, solidification and the dry mixed liquor, to obtain the nanosphere containing NADH or NADPH.
6. the preparation method of the nanosphere as claimed in claim 5 containing NADH or NADPH, which is characterized in that the colloidal sol
Or the heating temperature of the emulsion is 40~60 DEG C, heating time is 15~35min.
7. the preparation method of the nanosphere as claimed in claim 5 containing NADH or NADPH, which is characterized in that described in addition
After NADH or NADPH, 20min is stirred with the revolving speed of 1000-1500r/min, be added in the whipping process parts by weight be 0~
5 parts of stabilizer, the stabilizer include in vitamin E, chlorophyll, reproducibility ferredoxin and vitamin C at least
It is a kind of.
8. the preparation method of the nanosphere as claimed in claim 5 containing NADH or NADPH, which is characterized in that the cooling
It is cooled to 0~10 DEG C including the mixed liquor to be placed in ice-water bath, the temperature of the drying is not higher than 50 degree, the solidification
Process includes the pH of the mixed liquor being adjusted most 6~8, or the food that concentration is 1%~10% is added into the mixed liquor
Product add curing agent, the food additive add curing agent be in calcium chloride, calcium gluconate, calcium monohydrogen phosphate and calcium dihydrogen phosphate extremely
Few one kind.
9. a kind of pharmaceutical preparation includes the nanosphere and pharmacy according to any one of claims 1-4 containing NADH or NADPH
Upper acceptable auxiliary material.
10. pharmaceutical preparation as claimed in claim 9, which is characterized in that the pharmaceutical preparation be tablet, pulvis, capsule,
At least one of granula, pill, suspension, solution, syrup, mixture, powder, medicinal powder and dripping pill, it is described pharmaceutically
Acceptable auxiliary material includes at least one in mannitol, microcrystalline cellulose, magnesium stearate, carboxymethyl cellulose and calcium monohydrogen phosphate
Kind.
11. a kind of nanosphere according to any one of claims 1-4 containing NADH or NADPH is in treatment nervous system disease
Application in disease, diseases of cardiovascular and cerebrovascular systems.
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| CN201910237240.6A CN109908089A (en) | 2019-03-27 | 2019-03-27 | Nanosphere and the preparation method and application thereof containing NADH or NADPH |
| PCT/CN2020/080280 WO2020192557A1 (en) | 2019-03-27 | 2020-03-19 | Nadh or nadph-containing nano-microsphere and preparation method therefor and application thereof |
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| WO2020192557A1 (en) | 2020-10-01 |
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