CN109394701A - The bio-medical material and preparation method thereof for treating gastric ulcer - Google Patents
The bio-medical material and preparation method thereof for treating gastric ulcer Download PDFInfo
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- CN109394701A CN109394701A CN201811513493.3A CN201811513493A CN109394701A CN 109394701 A CN109394701 A CN 109394701A CN 201811513493 A CN201811513493 A CN 201811513493A CN 109394701 A CN109394701 A CN 109394701A
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- 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
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1664—Compounds of unknown constitution, e.g. material from plants or animals
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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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/10—Carbonates; Bicarbonates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
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- 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
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
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- 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
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
- A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Abstract
The present invention relates to a kind of bio-medical materials and preparation method thereof for treating gastric ulcer, are related to field of medicaments.The preparation method by the outer surface of pollen wall load calcium carbonate formed the first sample after, it is easy to operate, reliable in being coated with obtained by poly-dopamine for the first sample.It is provided by the invention treatment gastric ulcer bio-medical material, can gastric ulcer wound formed place play it is anti-oxidant, anti-inflammatory, in and gastric acid, inhibit ulcer increase the effect of.
Description
Technical field
The present invention relates to field of medicaments, and in particular to a kind of bio-medical material for treating gastric ulcer and its production side
Method.
Background technique
Gastric ulcer is a kind of common disease of digestive tract, be primarily referred to as stomach lining by peptic digest liquid autodigestion and caused by
More than the tissue damage of muscular layer of mucosa.The stress situation of the Crack cause of gastric ulcer and body, physics and chemical factor stimulation,
The infection of certain pathogens is related.
Existing gastric ulcer treatment method is mainly chemical medicinal treatment, and the problem of being primarily present is pair of the chemicals to stomach
Act on larger, there are adverse reactions, and treatment cycle is long；Traditional Chinese traditional medicine composition is more to the treatment method of gastric ulcer, but
It is that Chinese materia medica preparation is wide in variety, therapeutic effect otherness is big, and therapy mechanism is also unclear.
Bio-medical material is fast-developing in recent years, have been widely used for organism diagnosed, treated, being repaired or
Replace its disease damage tissue, organ.But the bio-medical material for being applied to gastric ulcer is actually rare, in view of this, special propose this
Invention.
Summary of the invention
Based on the above issues, the embodiment of the present invention provide it is a kind of for treating the bio-medical material of gastric ulcer, energy
Enough be adhered to mucous membrane and skin surface, can gastric ulcer wound formed place play it is anti-oxidant, anti-inflammatory, in and gastric acid, suppression
The effect of ulcer processed increases.
The embodiment of the present invention provides a kind of for treating the preparation method of the bio-medical material of gastric ulcer, operation letter
It is single, reliable, obtain can gastric ulcer wound formed place play it is anti-oxidant, anti-inflammatory, in and gastric acid, the function that inhibits ulcer to increase
The bio-medical material of the treatment gastric ulcer of effect.
The present invention solves its technical problem and adopts the following technical solutions to realize.
The embodiment of the present invention proposes a kind of for treating the preparation method of the bio-medical material of gastric ulcer, preparation step
Include:
Calcium carbonate is loaded in the outer surface of pollen wall, forms the first sample.
First sample is mixed with the alkalescent buffer containing dopamine, makes the first sample using the autohemagglutination of dopamine
It is coated with poly-dopamine.
Wherein, pollen wall is the natural pollen outer wall with cavity structure, and pollen wall has the conveying being connected to cavity logical
Road.
The embodiment of the present invention proposes a kind of bio-medical material for treating gastric ulcer, by above-mentioned for treating gastric ulcer
The preparation method of bio-medical material is made.
The embodiment of the present invention proposes a kind of bio-medical material for treating gastric ulcer comprising the first sample and is wrapped in
The poly-dopamine of first sample surfaces, the first sample include having the pollen wall of cavity structure and being at least carried on pollen wall
Outer surface calcium carbonate, pollen wall be the natural pollen outer wall with cavity structure, pollen wall have be connected to cavity it is defeated
Send channel.
The beneficial effect of the bio-medical material for the treatment of gastric ulcer of the embodiment of the present invention and preparation method thereof is:
Using the natural pollen outer wall with adhesive capacity as carrier, in carrier surface adheres to one layer of calcium carbonate, reaches
And gastric acid, slow down the effect of gastric ulcer, then calcium carbonate surface is adhered into a strata dopamine, poly-dopamine has anti-inflammatory, antioxygen
Change, the effect of mucoadhesive, to achieve the effect that alleviation and treatment treatment gastric ulcer.
Detailed description of the invention
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below will be to needed in the embodiment attached
Figure is briefly described, it should be understood that the following drawings illustrates only certain embodiments of the present invention, therefore is not construed as pair
The restriction of range for those of ordinary skill in the art without creative efforts, can also be according to this
A little attached drawings obtain other relevant attached drawings.
Fig. 1 is the SEM figure for the heronsbill conidia powder outer wall that the embodiment of the present invention 1 provides；
Fig. 2 is the SEM figure for the first sample that the embodiment of the present invention 2 provides；
Fig. 3 is the SEM figure for the bio-medical material for treating gastric ulcer that the embodiment of the present invention 2 provides；
Fig. 4 is that the mouse ethyl alcohol that test example 2 of the present invention provides causes stomach-filling pDA@CaCO after gastric ulcer3Stomach after@SEC 4h
HE dyes picture；
Fig. 5 is that gastric ulcer mouse caused by the ethyl alcohol that provides of test example 2 of the present invention gives after different pharmaceutical stomach HE after 14 days
Figure.
Specific embodiment
It in order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below will be in the embodiment of the present invention
Technical solution be clearly and completely described.The person that is not specified actual conditions in embodiment, according to normal conditions or manufacturer builds
The condition of view carries out.Reagents or instruments used without specified manufacturer is the conventional production that can be obtained by commercially available purchase
Product.
The bio-medical material and preparation method thereof of the treatment gastric ulcer of the embodiment of the present invention is specifically described below.
The present invention provides a kind of for treating the preparation method of the bio-medical material of gastric ulcer, and preparation step includes:
S1. calcium carbonate is loaded in the outer surface of pollen wall, forms the first sample.
Wherein, it should be noted that the pollen wall mentioned in the present invention is the natural pollen outer wall with cavity structure,
The main component of exposore is sporopollenin, and anticorrosive and anti acid alkali performance can be strong, is referred to below with pollen wall.Pollen wall has
Multiple transfer passages being connected to cavity.The outer surface of exposore has protrusion, such as semicircle, thorn-like or irregular convex
Rise etc., it that is to say that its outer surface is coarse surface, convenient for later period load calcium carbonate and poly-dopamine, while gastric ulcer occurs
Afterwards, gastric mucosa surface structure is destroyed, and inflammatory cell largely appears in the position of gastric ulcer formation, the structure energy of exposore
It is enough adhered on gastric mucosa, reaches target drug-carrying, and then carry out targeted therapy.
Wherein, it in order to enable the effect for the treatment of gastric ulcer is good, at gastric ulcer or the stimulation of mucous membrane etc. is smaller, does not cause
Burden, optionally, the partial size of pollen wall are 4-150 μm, for example, the partial size of pollen wall is 10 μm, 20 μm, 30 μm, 40 μm, 50 μm,
70 μm, 90 μm, 100 μm, 120 μm or 140 μm etc., preferably 10-120 μm, convenient for the biology doctor of operation preparation treatment gastric ulcer
Use material.
In embodiment provided by the invention, optionally, pollen is selected from heronsbill pollen, rape petal pollen, pollen pini and five
At least one of taste pollen, such as pollen are the mixed of heronsbill pollen, Schisandra chinensis pollen or rape petal pollen and pollen pini
Close object etc..Above-mentioned material is readily available.
Wherein, it should be noted that pollen wall provided by the invention can directly be bought in market, can also voluntarily be made
It is standby, optionally, in the present embodiment preferred embodiment, the preparation method of pollen wall include: at 50-80 DEG C, 300-900rpm's
Under the conditions of, the pollen after degreasing is reacted into 5-20h through acid or alkali, extremely with each cleaning of Hou Jingshui, acetone, hydrochloric acid and ethyl alcohol difference
Few 1 gained.Wherein, it under conditions of above-mentioned temperature and stirring rate, reacts, sufficiently effective can remove through acid or alkali
As long as ingredient is the ingredients such as endhymenine and the protein of pecto-cellulose, while being distinguished through water, acetone, hydrochloric acid and ethyl alcohol
Each cleaning, effectively removes above-mentioned substance, obtains more pollen wall.In the present invention, at least once be, for example, once, twice, three times,
Four times or five inferior.
Optionally, for the impurity that the pollen wall reduced as far as possible contains, the sequence of cleaning are as follows: through water, acetone, salt
Acid, water, acetone, ethyl alcohol successively clean at least once, water, acetone, hydrochloric acid and ethyl alcohol temperature be 40-60 DEG C；It that is to say
It is successively cleaned at least once using hot water, hot acetone, hot hydrochloric acid, hot water, hot acetone, hot ethanol.After the completion of cleaning, drying
Obtain dry pollen wall, spare or direct use.
It should be noted that the pollen after degreasing can directly be bought market, can also voluntarily prepare.It voluntarily prepares and for example adopts
With taking using the modes such as ether extraction, supercritical extract, for example, by using the mode that ether extracts, specifically: take dry pollen
Ether is added as solvent in grinding, and 600rpm is stirred overnight at room temperature, wherein the ratio between additive amount of pollen and ether is 10-30g:
170-250ml is washed repeatedly, 50-70 DEG C of drying using removing ether is filtered after reaction with ether.
Due to pollen wall acid-fast alkali-proof, in preferred embodiments of the present invention, carbonic acid is loaded in the outer surface of pollen wall
Before the step of calcium, further includes containing effective component in cavity through transfer passage, effectively prevent effective component in transport
It is degraded, while can be discharged from transfer passage, that is to say has sustained release in calcium carbonate after stomach decomposition in the process
Effect guarantees that effective component long-acting in target location, improves the effect for the treatment of.It should be noted that will through transfer passage
Effective component is contained is in the premise in cavity, and the partial size of effective component needs to be less than the maximum delivery area of transfer passage, just
Transfer passage, which is passed through, in effective component enters cavity.
Wherein, through channel by effective component contain in the method in cavity include the modes such as vacuum, high pressure and turbine into
Effective component in preferred embodiments of the present invention, is contained through transfer passage and includes: in the method in cavity by row
Pollen wall is uniformly mixed with the solution of effective component, places 0.5- under 2-8 DEG C, the vacuum condition of 10-20pa
5h；Effective component can effectively be contained in cavity.
Wherein, optionally, effective component is selected from growth factor, the pharmaceutical grade protein for treating gastric ulcer and for treating
At least one of compound medicine of gastric ulcer, wherein it should be noted that acid nonfast effective component can also be in this hair
In bright range of choice.
Growth factor for example can for human body Basic Fibroblast Growth Factor (bFGF), keratinocyte growth factor (KGF),
Epithelical cell growth factor (EGF), nerve growth factor (NGF), corium growth factor (AFGF), human fibroblastic growth factor
Son at least one of -21 (FGF-21) and human fibroblastic growth factor -9 (FGF-9), for treating the albumen of gastric ulcer
Matter and compound for treating gastric ulcer do not do specific restriction herein, can directly buy in market.
In preferred embodiments of the present invention, effective component is growth factor, preferably basic fibroblast growth factor；
Basic fibroblast growth factor effectively facilitates healing and tissue repair, the promotion regeneration and mind of gastric mucosa damage etc.
Through developing tissue growth, promote the effect for the treatment of gastric ulcer.
In order to further increase the load capacity of subsequent calcium carbonate etc., the purpose of gastric ulcer is alleviated in enhancing, and the present invention is preferable
In embodiment, effective component is contained before in cavity, further includes being dispersed in water pollen wall, is lyophilized.
In preferred embodiments of the present invention, optionally, the load capacity of effective component is the 1%-50% of pollen wall quality；Example
The load capacity of such as effective component is 1%, 5%, 10%, 20%, 30%, 40% or the 50% of pollen wall quality.
After being formed due to gastric ulcer, there is ulcer point in gastric mucosa structural damage, and gastric acid acidity can be made in pH=1.2 or so
Calcium carbonate is loaded at the aggravation of gastric ulcer degree, therefore in the outer surface of pollen wall, calcium carbonate is decomposed into Ca in acid condition2+
And CO2, alleviate damage of the gastric acid to ulcer, while calcium carbonate can neutralize gastric acid, body of stomach enable to reach neutral environment, protection has
Effect ingredient can reach gastric ulcer position, achieve the effect that treatment.
The step of outer surface of pollen wall loads calcium carbonate can for pollen wall is placed in solubility calcium salting liquid, then
Be added carbonate solution reacted, or pollen wall is placed in carbonate solution, be added solubility calcium salting liquid into
Row reacts, and includes: to be placed in pollen wall in the step of outer surface of pollen wall loads calcium carbonate in preferred embodiments of the present invention
In solubility calcium salting liquid, carbonate solution is added and is reacted；It can make Ca under this condition2+Suction-operated through pollen wall is attached
In the outer surface of pollen wall, carry out reaction in the outer surface of pollen wall and generate calcium carbonate, obtained calcium carbonate is in pollen wall
Outer surface is evenly distributed, and then the effect of subsequent targeted therapy is good.
In preferred embodiments of the present invention, the condition that carbonate solution is added includes: the stirring rate 200- at 2-8 DEG C
Carbonate solution is added under conditions of being 1-9mL/h in 500rpm, flow velocity；Under this condition, the calcium carbonate that can make is with particle
Form generate, be attached to the surface of pollen wall, while calcium carbonate more can be generated uniformly in the outer surface of pollen wall, into
And the effect of subsequent targeted therapy is good.
In preferred embodiments of the present invention, carbonate is at least one of sodium carbonate, ammonium hydrogen carbonate and potassium carbonate；This hair
In bright preferred embodiment, soluble calcium salt is selected from least one of calcium chloride and calcium nitrate.
In preferred embodiments of the present invention, calcium carbonate is in the 5%- that the load capacity of the first sample is first sample quality
20%, such as 5%, 7%, 10%, 12%, 15%, 18% or 20% etc..
S2. the first sample is mixed with the alkalescent buffer containing dopamine, makes the first sample using the autohemagglutination of dopamine
Product are coated with poly-dopamine.
Dopamine is a kind of good biocompatibility, the compound with stronger adhesive capacity, and dopamine has antioxygen
Change, anti-inflammatory efficacy, the reparation of gastric ulcer, the adhesion property of dopamine and the structure feature of pollen wall can be promoted, can be reached
Dual adhesiving effect.The generation of poly-dopamine is not only with the beneficial effect of dopamine, while effective protection treats gastric ulcer
Bio-medical material is during conveying, calcium carbonate and the premature release of effective component, and the effect of targeting quality is not achieved.
In preferred embodiments of the present invention, the reaction condition of the autohemagglutination of dopamine includes:
It is protected from light 1-5h under conditions of 1-8 DEG C, 100-500rpm, under this condition, poly-dopamine reaction effect is good, packet
It wraps up in completely, and then effectively prevent calcium carbonate and the premature release of effective component.
In preferred embodiments of the present invention, alkalescent buffer is the Tris buffer that pH value is 8-9, and dopamine is in Tris
The concentration of addition in buffer is 1-5mg/ml.
The present invention also provides a kind of bio-medical materials for treating gastric ulcer, by that can be used to treat gastric ulcer by above-mentioned
The preparation method of bio-medical material be made, can also be prepared using other methods, however, adopt how, most
The bio-medical material of the treatment gastric ulcer obtained afterwards includes the first sample and is wrapped in the first sample surfaces in structure
Poly-dopamine, the first sample includes the natural pollen wall with cavity structure and the outer surface for being at least carried on pollen wall
Calcium carbonate, pollen wall is the natural pollen outer wall with cavity structure, and pollen wall has the transfer passage that is connected to cavity, defeated
Send the quantity in channel for one or at least two, it is not limited here.
It holds, the present invention uses the natural pollen extract with adhesive capacity as drug or protein carrier, in carrier
One layer of calcium carbonate is adhered on surface, reaches neutralization gastric acid, slows down the effect of gastric ulcer, then calcium carbonate surface is adhered to a strata DOPA
Amine, poly-dopamine have the function of anti-inflammatory, anti-oxidant, mucoadhesive, to achieve the effect that a variety for the treatment of gastric ulcer.
Further include containing in the effective component in cavity in preferred embodiments of the present invention, effective component be selected from growth because
At least one of son, the pharmaceutical grade protein for treating gastric ulcer and compound medicine for treating gastric ulcer.
It that is to say, for protein medicaments or not acidproof drug is easy the phenomenon that inactivating in gastric acid environment, by albumen
Class drug or not acidproof drug and other drugs and pollen wall, calcium carbonate and polyacrylic acid for being used to treat gastric ulcer
Cooperation further achievees the effect that various ways treat gastric ulcer, it should be noted that, for treating the bio-medical material of gastric ulcer
Expect subsequent needs cryo-conservation under conditions of 2-7 DEG C.
Feature and performance of the invention are described in further detail with reference to embodiments.
Embodiment 1
The extraction of heronsbill conidia powder outer wall (SEC)
The extraction of 1.1 degreasing heronsbill pollen
200ml ether is added in round-bottomed flask in the heronsbill pollen for taking 20g dry, and 600rpm is stirred overnight at room temperature, and filters
Ether is removed, is washed three times with ether, 60 DEG C of dryings, room temperature preservation.
The extraction of 1.2 heronsbill conidia powder outer walls (SEC)
10g degreasing heronsbill pollen is taken, is ground, 150mL85% phosphoric acid is added and is reacted under conditions of 600rpm at 70 DEG C
10h, with 200mL hot water wash 3 times, 100mL hot acetone is washed twice, and the hot HCl of 100mL 2M is washed 2 times, and 200mL hot water wash 3 times,
100mL hot acetone is washed twice, and 100mL hot ethanol is washed twice, after obtain yellow solid particle, 60 DEG C of drying obtain brown
The electron-microscope scanning figure of SEC, SEC are shown in Fig. 1.
As seen from Figure 1, the surface SEC covers bayonet fittings, and in nature, bayonet fittings have strong adhesion energy
Power can be adhered to insect leg or body surface, achieve the purpose that pollination.Gastric ulcer occur after, gastric mucosa surface structure by
It destroys, inflammatory cell largely appears in the position of gastric ulcer formation, and the structure of SEC can be adhered on gastric mucosa, reaches targeting
Carry the effect of medicine.
Embodiment 2
For treating the preparation method of the bio-medical material of gastric ulcer, it is made by following methods:
1. the preparation of the first sample
Take SEC made from 2mg embodiment 1, by its 0.2mL concentration be 0.1M CaCl2It is uniformly dispersed, then with injection
Pump injection 0.2mL concentration is 0.05M Na2CO3, in 150rpm, 4 DEG C, react under the reaction condition of injection speed 0.5mL/min
1min, after reaction with 12000rpm, 4min centrifugation is removed supernatant, is then washed 1 time with 0.2mL deionization, collects solid
Freeze-drying is the first sample of light brown.
Fig. 2 is the scanning electron microscope (SEM) photograph of the first sample, it can be observed that there is one layer of calcium carbonate adherency on the surface SEC, calcium carbonate can
To reach neutralization gastric acid, alleviate the effect of gastric ulcer, maintains bFGF activity, have the function that protein medicaments therapeutic effect.
2. the preparation for the bio-medical material for treating gastric ulcer
It takes 4mg dopamine to be dissolved in the tris-buffer buffer solution of 2mL pH 8.4, the first sample of 2mg is added, point
It dissipates uniformly, at 4 DEG C, stirring rate is protected from light 3h under conditions of being 100rmp.After reaction, 4min is centrifuged with 1200rmp,
Supernatant is removed, is washed 2 times with 0.2mL deionization, is lyophilized to get grey black for treating the bio-medical material of gastric ulcer.
Fig. 3 is the scanning electron microscope (SEM) photograph for treating the bio-medical material of gastric ulcer, it can be observed that the biology for the treatment of gastric ulcer
The surface of medical material has and can adhere to poly-dopamine, and pollen bayonet fittings shorten, and treat the biomedical material surface of gastric ulcer
PDA have the function of anti-oxidant, anti-inflammatory, adherency pair, target administration can be reached, rush to adherency of the material to stomach surface is promoted
The effect of being repaired into gastric ulcer.
Embodiment 3
For treating the preparation method of the bio-medical material of gastric ulcer, it is made by following methods:
1. containing the preparation of the SEC of bFGF in cavity
SEC made from 5mg embodiment 1 is taken, addition 2ml water dispersion is uniform, is lyophilized after -20 DEG C of frosts.Then it will obtain
0.1mL concentration 5mg/mL bFGF solution is added in SEC, and ultrasound is uniformly mixed solution, 4 DEG C in the vacuum oven of 10-20pa
Vacuum 2h makes bFGF enter SEC cavity structure through transfer passage, and 12000rpm after vacuum, 4min centrifugation are removed supernatant, used
0.1mL deionization is washed 1 time, and precipitating is lyophilized after collecting, and have leisure the intracavitary SEC for containing bFGF.
2. the preparation of the first sample
Take the SEC that bFGF is contained in 2mg cavity, by its 0.2mL concentration be 0.1M CaCl2It is uniformly dispersed, then uses
Ejection of syringe pump 0.2mL concentration is 0.05M Na2CO3, 4 DEG C, anti-under the reaction condition of injection speed 0.2mL/min in 150rpm
1min is answered, after reaction with 12000rmp, 4min centrifugation is removed supernatant, then washed 1 time with 0.2mL deionization, collects shallow
The solid freeze-drying of brown is the first sample.
3. the preparation for the bio-medical material for treating gastric ulcer
It takes 4mg dopamine to be dissolved in the tris-buffer buffer solution of 2mL pH 8.4, the first sample of 2mg is added, point
It dissipates uniformly, at 4 DEG C, stirring rate is protected from light 3h under conditions of being 100rmp.After reaction, 4min is centrifuged with 1200rmp,
Supernatant is removed, is washed 2 times with 0.2mL deionization, is lyophilized to get grey black for treating the bio-medical material of gastric ulcer.
Embodiment 4
For treating the preparation method of the bio-medical material of gastric ulcer, it is made by following methods:
1. containing the preparation of the SEC of bFGF in cavity
SEC made from 4mg embodiment 1 is taken, addition 2ml water dispersion is uniform, is lyophilized after -20 DEG C of frosts.Then it will obtain
0.12mL concentration 5.5mg/mL bFGF solution is added in SEC, and ultrasound is uniformly mixed solution, 4 DEG C in the vacuum oven of 10pa
Vacuum 2.5h makes bFGF enter SEC cavity structure through transfer passage, and 12000rpm is centrifuged 3.5min centrifugation and goes after vacuum
Clear liquid is washed 1 time with 0.1mL deionization, and precipitating is lyophilized after collecting, and have leisure the intracavitary SEC for containing bFGF.
2. the preparation of the first sample
Take the SEC that bFGF is contained in 2mg cavity, by its 0.2mL concentration be 0.1M CaCl2It is uniformly dispersed, then uses
Ejection of syringe pump 0.2mL concentration is 0.05M Na2CO3, 5 DEG C, anti-under the reaction condition of injection speed 0.7mL/min in 160rpm
2min is answered, 4min is centrifuged with 12000rmp after reaction, removes supernatant, is then washed 1 time with 0.2mL deionization, is collected solid
Body freeze-drying is the first sample.
3. the preparation for the bio-medical material for treating gastric ulcer
It takes 3.8mg dopamine to be dissolved in the tris-buffer buffer solution of 2mL pH 8.4, the first sample of 2.1mg is added
Product are uniformly dispersed, and at 4.5 DEG C, stirring rate is protected from light 3h under conditions of being 100rmp.After reaction, with 1200rmp from
Heart 4min, removes supernatant, with 0.2mL deionization wash 2 times, freeze-drying to get.
Embodiment 5
The present embodiment the difference is that only step 1 with embodiment 3, and SEC made from 5mg embodiment 1 is taken to be directly added into
0.1mL concentration 5mg/mL bFGF solution, ultrasound are uniformly mixed solution, 4 DEG C of vacuum 2h in the vacuum oven of 10-20pa
BFGF is set to enter SEC cavity structure, supernatant is removed in 12000rpm after vacuum, 4min centrifugation, with 0.1mL deionization washing 1
Secondary, precipitating is lyophilized after collecting, the SEC for the intracavitary brown for containing bFGF of having leisure.
Embodiment 6
The present embodiment the difference is that only that the pollen used is pollen pini with embodiment 1.
Test example 1
The preparation method of the bio-medical material of gastric ulcer will be used to treat made from embodiment 2, by EDS energy spectrum diagram,
The first sample made from SEC made from embodiment 1, embodiment 2 is respectively obtained (with CaCO in the present invention3@SEC is indicated) and it is real
The bio-medical material obtained for treating gastric ulcer of example 2 is applied (with pDA@CaCO in the present invention3@SEC indicate) in element
Content, the results are shown in Table 1.
1 constituent content of table
| Constituent content | C | O | Ca |
| SEC | 38.9 | 61.1 | - |
| CaCO3@SEC | 27.9 | 64.93 | 7.66 |
| pDA@CaCO3@SEC | 33.26 | 60.74 | 6.01 |
PDA@can be proved it can be found that Ca constituent content reduces after the first sample adheres to upper pDA on surface according to table 1
CaCO3@SEC is constructed successfully.
Meanwhile embodiment 3-5 is tested respectively using which, it as a result finds, the calcium content in the first sample
Highest, in attachment after pDA, Ca constituent content is reduced, and illustrates that the structure for treating the bio-medical material of gastric ulcer is configured to function.
Content of the content of the calcium constituent loaded simultaneously through EDS energy spectrum diagram comparative analysis, embodiment 3 than the calcium constituent that embodiment 5 loads
It is more, illustrate the load for being conducive to calcium carbonate the step of freeze-drying.
Test example 2
1. mouse ethyl alcohol causes stomach-filling after gastric ulcer to give pDA@CaCO3The test of@SEC
Take babl/c small white mouse 5 of 4 months or so 20-30g, under the conditions of having abundant water resources it is hungry for 24 hours, by stomach-filling 75%
Ethyl alcohol 0.2ml forms acute gastric ulcer model.2h mouse gives pDA@CaCO made from 10mg/ml embodiment 2 through stomach-filling3@
After SEC 0.2ml, 4h, mouse, which takes off after neck is put to death, takes stomach, and gastric tissue is fixed with 4% paraformaldehyde, and alcohol is dehydrated step by step, paraffin packet
It buries, histotomy, about 5 μm of thickness.It is dyed after histotomy with HE staining kit, coloration result such as Fig. 4.
As a result as shown in Figure 4.Wherein Fig. 4 A and Fig. 4 B is that mouse ethyl alcohol causes stomach-filling pDA@CaCO after gastric ulcer3After@SEC
The HE of different parts dyes picture, is can be seen that in HE dyeing from arrow locations in Fig. 4 A and Fig. 4 B it can clearly be seen that stomach is burst
There is the deposition of the bio-medical material particle for treating gastric ulcer in ulcer region, and is adhered to gastric ulcer region, it was demonstrated that the material
It with good adhesive attraction, and can be enriched in surface of a wound region, reach better drug delivery effect.
2. different pharmaceutical is to the therapeutic effect of gastric ulcer mouse
Babl/c small white mouse 30 of 4 months or so 20-30g are taken, are randomly divided into 5 groups, it is hungry under the conditions of having abundant water resources
24h.Hungry mouse randomly select 4 groups after through 75% ethyl alcohol 0.2ml of stomach-filling formed gastric ulcer model；One group is given 0.2ml physiology
Salt water, as Normal group.0.2ml physiological saline is given in stomach-filling after Normal group mouse 2h.4 groups of gastric ulcer model mouse
After 2h, one group is given physiological saline 0.2ml by stomach-filling, and one group is given 0.4mg/ml bFGF 0.2ml by stomach-filling, and one group logical
It crosses stomach-filling and gives pDA@CaCO made from 10mg/ml embodiment 23@SEC 0.2ml, one group is given 10mg/ml by stomach-filling
pDA@CaCO3@SEC@bFGF(pDA@CaCO3@SEC@bFGF is that embodiment 3 is obtained for treating the bio-medical material of gastric ulcer
Material, every mg pDA@CaCO3@SEC@bFGF is containing about bFGF 40ug) 0.2ml.The every two days gastric infusions of mouse are primary, and 7 times altogether,
14 days mouse, which take off after neck is put to death, takes stomach, and gastric tissue is fixed with 4% paraformaldehyde, and alcohol is dehydrated step by step, and paraffin embedding, tissue is cut
Piece, about 5 μm of thickness.It is dyed after histotomy with HE staining kit, coloration result such as Fig. 5.
Fig. 5 is that gastric ulcer mouse caused by ethyl alcohol gives after different pharmaceutical that stomach HE schemes after 14 days.In Fig. 5, (a) is normal small
The HE image of mouse stomach；(b) stomach HE image after physiological saline is given for gastric ulcer mouse；(c) after giving bFGF for gastric ulcer mouse
Stomach HE image；(d) pDA@CaCO is given for gastric ulcer mouse3Stomach HE image after@SEC；(e) pDA@is given for gastric ulcer mouse
CaCO3Gastric tissue HE image after@SEC@bFGF.
From fig. 5 it becomes apparent that stomach, which is also in, repairs interim, stomach after gastric ulcer mouse gives physiological saline and bFGF
There is macroscopic-void (at arrow) between histocyte, and gastric ulcer mouse gives pDA@CaCO3There is a small amount of sky after@SEC, between gastric tissue
Hole, and cell arrangement is neat, gastric ulcer mouse gives pDA@CaCO3After@SEC@bFGF, gastric tissue is repaired preferably, several in tissue
And row histocyte small without cavity arranges compact, good effect.
The pDA@CaCO provided using embodiment 4 and embodiment 53The pDA@that@SEC@bFGF alternate embodiment 3 provides
CaCO3@SEC@bFGF, is tested according to the method described above, it is almost the same to obtain experimental result: gastric tissue is repaired preferably, tissue
In almost without cavity it is small and row histocyte column it is compact.By above-mentioned test it is contemplated that the embodiment of the present invention mentions
The bio-medical material of the treatment gastric ulcer of confession also has the effect of alleviation and treatment treatment gastric ulcer to human body.
To sum up, the bio-medical material of the treatment gastric ulcer of the offer of the embodiment of the present invention is with the natural of adhesive capacity
Pollen wall adheres to one layer of calcium carbonate as carrier, in carrier surface, reaches neutralization gastric acid, slows down the effect of gastric ulcer, then by carbon
A strata dopamine is adhered on sour calcium surface, and poly-dopamine has the function of anti-inflammatory, anti-oxidant, mucoadhesive, to reach alleviation
And the effect for the treatment of treatment gastric ulcer.The preparation method of the above-mentioned bio-medical material for being used to treat gastric ulcer, preparation method
Simply, reliably, obtain can gastric ulcer wound formed place play it is anti-oxidant, anti-inflammatory, in and gastric acid, inhibit ulcer increase
The bio-medical material of the treatment gastric ulcer of effect.
Embodiments described above is a part of the embodiment of the present invention, instead of all the embodiments.Reality of the invention
The detailed description for applying example is not intended to limit the range of claimed invention, but is merely representative of selected implementation of the invention
Example.Based on the embodiments of the present invention, 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.
Claims (10)
1. a kind of for treating the preparation method of the bio-medical material of gastric ulcer, which comprises the steps of:
Calcium carbonate is loaded in the outer surface of pollen wall, forms the first sample；
First sample is mixed with the alkalescent buffer containing dopamine, makes described using the autohemagglutination of the dopamine
A sample is coated with poly-dopamine；
Wherein, the pollen wall is the natural pollen outer wall with cavity structure, and the pollen wall has to be connected to the cavity
Transfer passage.
2. according to claim 1 for treating the preparation method of the bio-medical material of gastric ulcer, which is characterized in that
It further include containing effective component through the transfer passage before the outer surface of the pollen wall loads the step of calcium carbonate
In the cavity, the effective component is selected from growth factor, the pharmaceutical grade protein for treating gastric ulcer and for treating stomach
At least one of compound medicine of ulcer；
Preferably, the effective component is growth factor, preferably basic fibroblast growth factor；
Preferably, effective component is contained method in the cavity through the transfer passage includes:
The pollen wall is uniformly mixed with the solution of the effective component, is placed under 2-8 DEG C, the vacuum condition of 10-20pa
0.5-5h；
Preferably, the load capacity of the effective component is the 1%-50% of the pollen wall quality；
It preferably, further include dispersing water for the pollen wall before the step of effective component being contained in the cavity
In, freeze-drying.
3. according to claim 1 for treating the preparation method of the bio-medical material of gastric ulcer, which is characterized in that
The outer surface of the pollen wall loads the step of calcium carbonate and includes:
The pollen wall is placed in solubility calcium salting liquid, carbonate solution is added and is reacted；
Preferably, the condition that the carbonate solution is added includes: stirring rate 200-500rpm, flow velocity 1- at 2-8 DEG C
The carbonate solution is added under conditions of 9mL/h；
Preferably, the carbonate is at least one of sodium carbonate, ammonium hydrogen carbonate and potassium carbonate；
Preferably, the soluble calcium salt is selected from least one of calcium chloride and calcium nitrate.
4. the preparation method of the bio-medical material for the treatment of gastric ulcer according to claim 1, which is characterized in that the carbon
Sour calcium is in the 5%-10% that the load capacity of the first sample is the first sample quality.
5. according to claim 1 for treating the preparation method of the bio-medical material of gastric ulcer, which is characterized in that institute
The reaction condition for stating the autohemagglutination of dopamine includes:
1-5h is protected from light under conditions of 1-8 DEG C, 100-500rpm；
Preferably, the alkalescent buffer is the Tris buffer that pH value is 8-9, and the dopamine is in the Tris buffer
In addition concentration be 1-5mg/ml.
6. according to claim 1 for treating the preparation method of the bio-medical material of gastric ulcer described in -5 any one,
It is characterized in that, the preparation method of the pollen wall includes:
Under the conditions of 50-80 DEG C, 300-900rpm, by the pollen after degreasing through acid or alkali react 5-20h, with Hou Jingshui, acetone,
Hydrochloric acid and ethyl alcohol difference at least 1 time gained of each cleaning；
Preferably, the sequence of the cleaning are as follows: it is successively cleaned at least once through water, acetone, hydrochloric acid, water, acetone, ethyl alcohol, it is described
Water, the acetone, the hydrochloric acid and the ethyl alcohol temperature be 40-60 DEG C.
7. according to claim 1 for treating the preparation method of the bio-medical material of gastric ulcer described in -5 any one,
It is characterized in that, the partial size of the pollen wall is 4-150 μm, preferably 10-120 μm；
Preferably, the pollen is selected from least one of heronsbill pollen, rape petal pollen, pollen pini and Schisandra chinensis pollen.
8. a kind of bio-medical material for treating gastric ulcer, which is characterized in that its use as described in claim 1-7 any one
It is made in the preparation method of the bio-medical material for the treatment of gastric ulcer.
9. a kind of bio-medical material for treating gastric ulcer, which is characterized in that it includes the first sample and is wrapped in described
The poly-dopamine on a sample surface, first sample include having the natural pollen wall of cavity structure and being at least carried on
The calcium carbonate of the outer surface of the pollen wall, the pollen wall are the natural pollen outer wall with cavity structure, the pollen wall
With the transfer passage being connected to the cavity.
10. the bio-medical material for the treatment of gastric ulcer according to claim 9, which is characterized in that further include containing in institute
The effective component in cavity is stated, the effective component is selected from growth factor, the pharmaceutical grade protein for treating gastric ulcer and is used for
At least one of the compound medicine for treating gastric ulcer.
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| WO2020206813A1 (en) * | 2019-04-10 | 2020-10-15 | 大连理工大学 | Micro-particle having pollen structure, preparation method therefor and use thereof |
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