CN106361718A - Colon-specific bioadhesive tablet containing monosialotetrahexosyl ganglioside sodium - Google Patents
Colon-specific bioadhesive tablet containing monosialotetrahexosyl ganglioside sodium Download PDFInfo
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- A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
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Abstract
The invention provides a colon-specific bioadhesive tablet containing monosialotetrahexosyl ganglioside sodium. The colon-specific bioadhesive tablet comprises a tablet-loaded core and a coating wrapping the tablet-loaded core, wherein the tablet-loaded core is prepared from monosialotetrahexosyl ganglioside sodium and a pharmaceutical carrier, and the coating is mainly prepared from ethyl cellulose, zein, dibutyl phthalate, stevioside and mannitol. The colon-specific bioadhesive tablet containing monosialotetrahexosyl ganglioside sodium has the high colon-specific drug release degree; due to the fact that when the bioadhesive tablet is in the stomach and the small intestines, the release degree of the active ingredients of the drug is low, the risk that the active ingredients of the drug are degraded in the stomach is reduced, and the stability of the drug in the stomach and the small intestines is improved; when the bioadhesive tablet reaches the colon, the bioadhesive tablet starts releasing the active ingredients of the drug, and therefore the pharmaceutical effect of the bioadhesive tablet is improved.
Description
Technical field
The invention belongs to pharmaceutical technology field, the colon target of more particularly, to a kind of GM1
To biological adhesive tablet.
Background technology
Ganglioside be family's isomery containing sialic baroque membrane glycolipid matter, have raising neuranagenesis,
Promote the function of CO2 laser weld, can be used for the treatment of central nervous system's relevant disease.Monostalotetrahexosylgangliside
(gm1) it is an important class in ganglioside with the various biological effect such as neurotrophy and central nervous system's reparation,
Its effect in nervous system injury treatment is just in widespread attention.Monostalotetrahexosylgangliside molecule is by containing
The ceramide moiety of lipophilic and a hydrophilic sialyloligosaccharide group amphiphatic molecule dimerous, therefore have concurrently water-soluble
Property and fat-soluble two kinds of characteristics, can pass through blood brain barrier, concentrate on the embedded neuron membrane damaging, in the differentiation of neurocyte
Generate and improve it and deposit with growth, the plasticity of neuron, the transmission of synapse and the dendron to the post-traumatic neurocyte of increase
Functional rehabilitation after motility rate, the multiple reparations participating in different nerves and inducing neural regeneration and nervous system trauma has extremely
Important effect, for the traumatic central nervous system injury causing, the vascular nerve injury that ischemia or bleeding cause is all
There is obvious repair, and the behavior disorder caused by parkinson disease can be significantly improved.Monosialogangliosides glycosides
Fat is by clinic application in cerebrovascular disease, neuropathic pain, Ao Benhaimoshi disease, parkinson, central nervous system
Multiple sacred disease such as wound, wherein for treatment parkinson effect is significant, shows good curative effect.Current single saliva
Liquid acid tetrahexose ganglioside preparation is essentially injection, there is medicament transport high cost, easily damaged, administration inconvenient, no
The many, problems such as patient tolerability is poor, clinical risk height of good reaction, easy to use not as good as oral agents；But due to single saliva
Sour tetrahexose ganglioside sodium is unstable in gastrointestinal tract, is extremely easy in decomposition, in gastrointestinol microorganism and hydrolytic enzyme after being administered orally
Under decomposition, it is impossible to play curative effect, therefore urgent need is developed one kind and stably can be deposited in gastrointestinal tract for rapid forfeiture pharmacological action
And can effectively play the GM1 oral formulations of pharmacological action.One is disclosed in prior art
It is own that the oral formulations of a little Monostalotetrahexosylganglisides, such as cn201410849184.9 disclose a kind of single sialic acid four
The oral formulations of sugar ganglioside sodium, but this oral formulations stability is not good in the gastrointestinal tract, lead to therapeutic effect undesirable.
Content of the invention
In order to solve above-mentioned technical problem, the present invention provides a kind of colon target of GM1
To biological adhesive tablet, the coatings of load tablet core load described with the parcel tablet core being 30-40: 1 including ratio of weight and number, described
GM1 and the pharmaceutical carrier preparation of 15-30 part that load tablet core is 3-8 part by parts by weight
Form, described coatings are mainly prepared from by each component of following parts by weight:
The coatings of the biological adhesive tablet that the present invention provides can form layer protecting film, protection in the outer layer carrying tablet core
GM1 is not decomposed in the little enteral of harmonization of the stomach and loses medicinal effectiveness, and discharges single in colon
Sialic acid tetrahexose ganglioside sodium, thus improve the drug utilization effect of biological adhesive tablet.
Further, prepare each component that described coatings also include following parts by weight:
Pulullan polysaccharide 2-5
Titanium dioxide 0.5-2.
Add pulullan polysaccharide and titanium dioxide can improve the segmented intestine targeted of biological adhesive tablet further in coatings
The effect of release.
Further, prepare each component that described coatings also include following parts by weight:
Polymethyl methacrylate 3-5
D- xylose 1-2
Thioglucose 0.5-1.
Add polymethyl methacrylate, d- xylose and thioglucose can improve bioadhesion in biological adhesive tablet
Adhesiving effect on mucous membrane of colon for the piece, reduces or changes one of composition, and the colon adhesiving effect of biological adhesive tablet is deteriorated.
Further, prepare each component that described coatings also include following parts by weight:
Chitose 2-3
Sodium cholate 0.2-0.5.
Add chitose and sodium cholate to be remarkably improved the stability of biological adhesive tablet in coatings, reduce one of
Composition, or change one of composition, the stability of biological adhesive tablet declines.
Further, prepare each component that described coatings also include following parts by weight:
Carbomer 0.5-1
Dithioglycollic acid 0.1-0.3
Sodium potassium tartrate tetrahydrate 0.1-0.3.
Add Carbomer, dithioglycollic acid and sodium potassium tartrate tetrahydrate can effectively improve biological adhesive tablet in coatings
Hardness and friability.
Further, described pharmaceutical carrier includes each component of following parts by weight:
Medicinal using inclusion pregelatinized starch, silica sol, maltose alcohol, octaacetyl sucrose and calcium glycerophosphate
The load tablet core that carrier is prepared together with GM1 can extend biological adhesive tablet intracolic
Action time, extend the effective acting time of medicine.
Further, described pharmaceutical carrier also includes each component of following parts by weight:
Glycine 0.5-1.5
Ethylmaltol 0.2-0.5.
Add glycine and ethylmaltol can extend biological adhesive tablet further in intracolic work in pharmaceutical carrier
With the time, extend the effective time of biological adhesive tablet, reduce one of composition, or change one of composition, bioadhesion
The action time of piece shortens.
The present invention also provides a kind of preparation of the colon target biology adhesion tablet of GM1
Method, comprises the steps:
S1. by GM1 and pharmaceutical carrier mix homogeneously, add appropriate 35% ethanol molten
Liquid prepares soft material, pelletizes after 14 mesh sieves, crosses 20 mesh sieve granulate and obtains drug particles, drug particles are placed in tablet machine after being dried
Middle tabletting can obtain load tablet core；
S2. ethyl cellulose, zein, dibutyl phthalate, stevioside and Mannitol are added 2 times of quality
Mix homogeneously in 85% ethanol water, makes coating solution；
S3. put into carrying tablet core in fluidized-bed coating machine, just film-making can be obtained using coating solution coating 20-30min,
Then first film-making is placed in aging 24-48h in 45 DEG C of baking ovens and can obtain biological adhesive tablet.
Further, the coating parameter of described fluidized-bed coating machine is: 43-45 DEG C of temperature of charge, inlet temperature 60-65
DEG C, rotation speed of fan 28-30hz, atomizing pressure 0.18-0.2mpa, preheating time 5-10min.
The colon target biology adhesion tablet of GM1 provided by the present invention has very well
Colon-targeted delivery system, biological adhesive tablet be located at harmonization of the stomach little enteral when, the release of active constituents of medicine is relatively low, reduces medicine
The risk of the degraded in gastric for the thing active component, improves it in the enteral stability of harmonization of the stomach, and after reaching colon site, biological
Adhesion tablet starts to discharge active constituents of medicine again, improves the medicinal effects of biological adhesive tablet；And biological adhesive tablet has one
Fixed mucosa-adherent, can extend the time of staying on mucosa for the active constituents of medicine, increase medicine in colon local concentration, carry
High therapeutic effect.
Specific embodiment
Embodiment 1
A kind of colon target biology adhesion tablet of GM1, including load tablet core and parcel
The described coatings carrying tablet core, needed for 100 this biological adhesive tablets of preparation, the weight of each component is as follows:
Load tablet core:
GM1 3g
Pharmaceutical carrier 15g
Coatings:
Embodiment 2
A kind of colon target biology adhesion tablet of GM1, including load tablet core and parcel
The described coatings carrying tablet core, needed for 100 this biological adhesive tablets of preparation, the weight of each component is as follows:
Load tablet core:
GM1 8g
Pharmaceutical carrier 30g
Coatings:
The preparation method of described biological adhesive tablet comprises the steps:
S1. by GM1 and pharmaceutical carrier mix homogeneously, add appropriate 35% ethanol molten
Liquid prepares soft material, pelletizes after 14 mesh sieves, crosses 20 mesh sieve granulate and obtains drug particles, drug particles are placed in tablet machine after being dried
Middle tabletting can obtain load tablet core；
S2. ethyl cellulose, zein, dibutyl phthalate, stevioside and Mannitol are added 2 times of quality
Mix homogeneously in 85% ethanol water, makes coating solution；
S3. put into carrying tablet core in fluidized-bed coating machine, just film-making can be obtained using coating solution coating 20min, so
Afterwards first film-making is placed in aging 24h in 45 DEG C of baking ovens and can obtain biological adhesive tablet.
Embodiment 3
A kind of colon target biology adhesion tablet of GM1, including load tablet core and parcel
The described coatings carrying tablet core, needed for 100 this biological adhesive tablets of preparation, the weight of each component is as follows:
Load tablet core:
GM1 5g
Pharmaceutical carrier 20g
Coatings:
Embodiment 4
A kind of colon target biology adhesion tablet of GM1, as different from Example 1,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Embodiment 5
A kind of colon target biology adhesion tablet of GM1, as different from Example 2,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
The preparation method of described biological adhesive tablet comprises the steps:
S1. by GM1 and pharmaceutical carrier mix homogeneously, add appropriate 35% ethanol molten
Liquid prepares soft material, pelletizes after 14 mesh sieves, crosses 20 mesh sieve granulate and obtains drug particles, drug particles are placed in tablet machine after being dried
Middle tabletting can obtain load tablet core；
S2. ethyl cellulose, zein, dibutyl phthalate, stevioside and Mannitol are added 2 times of quality
Mix homogeneously in 85% ethanol water, makes coating solution；
S3. put into carrying tablet core in fluidized-bed coating machine, in the coating parameter of fluidized-bed coating machine be: temperature of charge 44
DEG C, 62 DEG C of inlet temperature, rotation speed of fan 29hz, atomizing pressure 0.19mpa, preheating time 8min process conditions under adopt coating
Liquid coating 25min can obtain just film-making, then first film-making is placed in aging 36h in 45 DEG C of baking ovens and can obtain bioadhesion
Piece.
Embodiment 6
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Embodiment 7
A kind of colon target biology adhesion tablet of GM1, as different from Example 1,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Embodiment 8
A kind of colon target biology adhesion tablet of GM1, as different from Example 5,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
The preparation method of described biological adhesive tablet comprises the steps:
S1. by GM1 and pharmaceutical carrier mix homogeneously, add appropriate 35% ethanol molten
Liquid prepares soft material, pelletizes after 14 mesh sieves, crosses 20 mesh sieve granulate and obtains drug particles, drug particles are placed in tablet machine after being dried
Middle tabletting can obtain load tablet core；
S2. ethyl cellulose, zein, dibutyl phthalate, stevioside and Mannitol are added 2 times of quality
Mix homogeneously in 85% ethanol water, makes coating solution；
S3. put into carrying tablet core in fluidized-bed coating machine, in the coating parameter of described fluidized-bed coating machine be: material temperature
Degree 45 DEG C, 65 DEG C of inlet temperature, rotation speed of fan 30hz, atomizing pressure 0.2mpa, preheating time 10min process conditions under adopt
Coating solution coating 30min can obtain just film-making, then first film-making is placed in aging 48h in 45 DEG C of baking ovens and can obtain biological slime
Radix Aconiti Lateralis Preparata.
Embodiment 9
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Embodiment 10
A kind of colon target biology adhesion tablet of GM1, as different from Example 1,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Embodiment 11
A kind of colon target biology adhesion tablet of GM1, as different from Example 8,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Embodiment 12
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Embodiment 13
A kind of colon target biology adhesion tablet of GM1, as different from Example 1,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Embodiment 14
A kind of colon target biology adhesion tablet of GM1, different from embodiment 11
It is that the weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Embodiment 15
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Embodiment 16
A kind of colon target biology adhesion tablet of GM1, as different from Example 1,
Needed for 100 this biological adhesive tablets of preparation, the weight of each component of pharmaceutical carrier is as follows:
Embodiment 17
A kind of colon target biology adhesion tablet of GM1, different from embodiment 14
It is that needed for 100 this biological adhesive tablets of preparation, the weight of each component of pharmaceutical carrier is as follows:
Embodiment 18
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
Needed for 100 this biological adhesive tablets of preparation, the weight of each component of pharmaceutical carrier is as follows:
Embodiment 19
A kind of colon target biology adhesion tablet of GM1, different from embodiment 16
It is that needed for 100 this biological adhesive tablets of preparation, the weight of each component of pharmaceutical carrier is as follows:
Embodiment 20
A kind of colon target biology adhesion tablet of GM1, different from embodiment 17
It is that needed for 100 this biological adhesive tablets of preparation, the weight of each component of pharmaceutical carrier is as follows:
Embodiment 21
A kind of colon target biology adhesion tablet of GM1, different from embodiment 18
It is that needed for 100 this biological adhesive tablets of preparation, the weight of each component of pharmaceutical carrier is as follows:
Reference examples 1
A kind of colon target biology adhesion tablet of GM1, including load tablet core and parcel
The described coatings carrying tablet core, needed for 100 this biological adhesive tablets of preparation, the weight of each component is as follows:
Load tablet core:
GM1 5g
Pharmaceutical carrier 20g
Coatings:
Reference examples 2
A kind of colon target biology adhesion tablet of GM1, including load tablet core and parcel
The described coatings carrying tablet core, needed for 100 this biological adhesive tablets of preparation, the weight of each component is as follows:
Load tablet core:
GM1 5g
Pharmaceutical carrier 20g
Coatings:
Reference examples 3
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Reference examples 4
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Reference examples 5
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Reference examples 6
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Reference examples 7
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Reference examples 8
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Reference examples 9
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Reference examples 10
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
The weight of each component needed for coatings of 100 this biological adhesive tablets of preparation is as follows:
Reference examples 11
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
Needed for 100 this biological adhesive tablets of preparation, the weight of each component of pharmaceutical carrier is as follows:
Reference examples 12
A kind of colon target biology adhesion tablet of GM1, as different from Example 3,
Needed for 100 this biological adhesive tablets of preparation, the weight of each component of pharmaceutical carrier is as follows:
Reference examples 13
A kind of colon target biology adhesion tablet of GM1, different from embodiment 18
It is that needed for 100 this biological adhesive tablets of preparation, the weight of each component of pharmaceutical carrier is as follows:
Reference examples 14
A kind of colon target biology adhesion tablet of GM1, different from embodiment 18
It is that needed for 100 this biological adhesive tablets of preparation, the weight of each component of pharmaceutical carrier is as follows:
Colon-targeted delivery system effect assessment
The biological adhesive tablet that testing example 3, embodiment 6, reference examples 1-4 provide and cn201410849184.9 carry respectively
For GM1 release performance in gastric juice, intestinal fluid and colonic fluid for the oral formulations, knot
Fruit is shown in Table 1.
Table 1 cumulative release amount (%) test result
| Group | Gastric juice (2h) | Intestinal fluid (6h) | Colonic fluid (6h) |
| Embodiment 3 | 5.2 | 9.4 | 85.3 |
| Embodiment 6 | 2.4 | 3.3 | 94.1 |
| Reference examples 1 | 58.3 | 25.9 | 15.3 |
| Reference examples 2 | 72.9 | 18.5 | 8.5 |
| Reference examples 3 | 5.0 | 9.1 | 85.8 |
| Reference examples 4 | 4.6 | 8.3 | 87.1 |
| cn200910217278 | 85.1 | 7.7 | 7.2 |
From the above results, the biological adhesive tablet that the present invention provides discharges less, baseset in gastric juice and intestinal fluid
In discharge in colonic fluid, the effect of its colon-targeted delivery system is significantly better than the biological adhesive tablet that reference examples 1 and reference examples 2 provide
And the oral formulations of the GM1 of cn201410849184.9 offer, illustrate that the present invention provides
Biological adhesive tablet coatings can carry tablet core outer layer formed layer protecting film, protection monosialyl tetrahexose nerve
Section glycosides fat sodium is not decomposed in the little enteral of harmonization of the stomach and loses medicinal effectiveness, and sustained release monosialyl tetrahexose is refreshing in colon
Warp knuckle glycosides fat sodium, thus improve the therapeutic effect of biological adhesive tablet.
Biological adhesive tablet and embodiment 3 that the embodiment of the present invention 6 provides, reference examples 3, the biological adhesive tablet phase of reference examples 4
Its burst size in gastric juice and intestinal fluid is less, illustrates to add pulullan polysaccharide and titanium dioxide can enter in coatings for ratio
One step improves the effect of the colon-targeted delivery system of biological adhesive tablet.
External biological adhesiveness effect assessment
Choose 12 healthy sprague-dawley male rats, body weight 140-160g, test prospective adaptation feeds one
In week, feeding environment temperature is 24 ± 1 DEG C, and humidity is 55 ± 5%, then puts to death after whole Rat Fast, taboo water 24h, takes knot
Mucous membrane of colon with normal saline flushing clean colon inwall, is then all opened and is laid on microscope slide, by 12 rats by intestinal
Mucous membrane of colon is uniformly divided into 4 groups at random, respectively test group and contrast test 1-3 group, the Colonic Mucosa of The Rat surface of test group
Uniformly sprinkle the biological adhesive tablet powder of 500mg embodiment 9 offer respectively, the Colonic Mucosa of The Rat surface of 1 group of comparison is respectively all
The even biological adhesive tablet powder sprinkling 500mg embodiment 3, the Colonic Mucosa of The Rat surface of 2 groups of comparison uniformly sprinkles 500mg respectively
The biological adhesive tablet powder that reference examples 5 provide, the Colonic Mucosa of The Rat surface of 3 groups of comparison uniformly sprinkles 500mg reference examples 6 respectively
The biological adhesive tablet powder providing, then whole Colonic Mucosa of The Rats is placed in the hermetic container of saturated nacl aqueous solution,
Moisturizing 20mi n, takes out microscope slide and is fixed on the flushed channel placed in 45 ° of oblique angles, (contained with phosphate buffer
0.56% dipotassium hydrogen phosphate, 0.04% potassium dihydrogen phosphate, ph7.8-8.0) as flushing liquor, adjust wriggling flow rate pump, with
The flow velocity of 0.1ml/s rinses 5min, collects flushing liquor (common 30ml), dries the meansigma methodss calculating every group after weighing, result such as table 2
Shown.
The mucous membrane of colon adhesion of biological adhesive tablet is represented with Percent Adhesion, and colon Percent Adhesion is bigger to represent adhesion
Power is bigger,
Colon Percent Adhesion (%)=[m- (g-g0- m)]/m × 100%
Wherein: the weight of the biological adhesive tablet powder that m- adds, g0- empty beaker weight, after g- beaker and drying, residue is total
Weight；The gross weight of solid matter contained by m- phosphate buffer
Table 2 external biological adhesion test result
| Group | Test group | 1 group of contrast test | 2 groups of contrast test | 3 groups of contrast test |
| Average colon Percent Adhesion (%) | 95.1 | 80.3 | 82.9 | 85.0 |
From the above results, the external biological adhesion of the biological adhesive tablet that embodiment 9 provides is significantly greater than embodiment
3rd, the biological adhesive tablet of reference examples 5 and reference examples 6 offer, illustrates to add polymethyl methacrylate, d- in biological adhesive tablet
Xylose and thioglucose can improve biological adhesive tablet adhesiving effect in colon, reduce or change one of composition, raw
The colon adhesiving effect of thing adhesion tablet is deteriorated.
Biological adhesive tablet estimation of stability
1. accelerated test
Example 3, the biological adhesive tablet of embodiment 12, reference examples 7 and reference examples 8, all at 40 DEG C ± 2 DEG C of temperature,
Relative humidity is to place 6 months under conditions of 75% ± 5%, 1 month during testing, 2 months, 3 months, 6 the end of month respectively
Sampling once, detects character, color and luster, abnormal smells from the patient, main constituent content (labelled amount %) and the moisture of biological adhesive tablet, it was found that
The indices of the biological adhesive tablet of embodiment 12 have no significant change；And the biological slime of embodiment 3, reference examples 7 and reference examples 8
Different degrees of moisture and increases and darken phenomenon in Radix Aconiti Lateralis Preparata.
2. long term test
Example 3, the biological adhesive tablet of embodiment 12, reference examples 7 and reference examples 8, all at 25 DEG C ± 2 DEG C of temperature,
Relative humidity be 60% ± 10% under conditions of place 12 months, 0 month during testing, 3 months, 6 months, 9 months, 12
The end of month is separately sampled once, the character of detection biological adhesive tablet, color and luster, main constituent content (labelled amount %) and moisture, and result is sent out
Existing, the indices of the biological adhesive tablet of embodiment 12 have no significant change；And the life of embodiment 3, reference examples 7 and reference examples 8
Different degrees of moisture and increases and darken phenomenon in thing adhesion tablet.
Knowable to the result of above-mentioned accelerated test and long term test, in biological adhesive tablet, addition chitose and sodium cholate can
Significantly improve the stability of biological adhesive tablet, reduce one of composition, or change one of composition, biological adhesive tablet steady
Qualitative decline.
Biological adhesive tablet friability is evaluated
According to the regulation in Chinese Pharmacopoeia, measure what embodiment 3, embodiment 15, reference examples 9 and reference examples 10 provided respectively
The friability of biological adhesive tablet, the results are shown in Table 3.
Table 3 biological adhesive tablet friability is evaluated
| Group | Less loss weight (%) | Outward appearance |
| Embodiment 15 | 0.15 | No fragment, fracture |
| Embodiment 3 | 1.8 | There are a little fragment and fracture |
| Reference examples 9 | 1.5 | There are a little fragment and fracture |
| Reference examples 10 | 1.1 | Somewhat fragment |
From the above results, add Carbomer, dithioglycollic acid and sodium potassium tartrate tetrahydrate permissible in biological adhesive tablet
Effectively improve hardness and the friability of biological adhesive tablet.
Biological adhesive tablet delivery evaluation in vivo
Take biological adhesive tablet (its that the embodiment of the present invention 3, embodiment 18, embodiment 21 and reference examples 11-14 provide respectively
The pharmaceutical carrier carrying in tablet core of the biological adhesive tablet that middle embodiment 3 provides adopts weight fraction to form sediment than the pregel for 2: 1
Powder and Microcrystalline Cellulose), put in medicament dissolution instrument, separately sampled in 1h, 2h, 4h, 8h, 12h, 18h, 24h, use high-efficient liquid phase color
Spectrometry detection biological adhesive tablet dissolution percentage rate, and calculate the cumulative release percentage rate of biological adhesive tablet, the results are shown in Table 4.
Cumulative release percentage rate (%) result of the test of table 4 biological adhesive tablet
| Group | 0h | 1h | 2h | 4h | 8h | 12h | 18h | 24h |
| Embodiment 3 | 0 | 52 | 75 | 95 | 100 | -- | -- | -- |
| Embodiment 18 | 0 | 36 | 58 | 75 | 86 | 94 | 100 | -- |
| Embodiment 21 | 0 | 20 | 35 | 49 | 61 | 75 | 87 | 97 |
| Reference examples 11 | 0 | 49 | 70 | 91 | 100 | -- | -- | -- |
| Reference examples 12 | 0 | 40 | 66 | 87 | 99 | 100 | -- | -- |
| Reference examples 13 | 0 | 34 | 54 | 74 | 83 | 92 | 100 | -- |
| Reference examples 14 | 0 | 32 | 50 | 67 | 79 | 90 | 100 | -- |
From above-mentioned result of the test, the biological adhesive tablet that the embodiment of the present invention 18 provides can continue slow in 18h
Release, and the biological adhesive tablet that embodiment 3 and reference examples 11 provide just discharges in 8h completely, the biological slime that reference examples 12 provide
Radix Aconiti Lateralis Preparata also discharges in 12h completely, illustrates that employing includes pregelatinized starch, silica sol, maltose alcohol, octaacetyl sucrose
The load tablet core prepared together with GM1 with the pharmaceutical carrier of calcium glycerophosphate can extend life
Thing adhesion tablet, in intracolic action time, extends the effective acting time of medicine.
The biological adhesive tablet that the embodiment of the present invention 21 provides can continue slowly to discharge more than 24h, and embodiment 18, comparison
The biological adhesive tablet of example 13 and reference examples 14 offer just discharges completely in 18h and finishes, and illustrates in the pharmaceutical carrier carrying tablet core
Middle addition glycine and ethylmaltol can extend biological adhesive tablet further in intracolic action time, extend bioadhesion
The effective time of piece, reduces one of composition, or changes one of composition, shortens the action time of biological adhesive tablet.
Finally it should be noted that above example is only in order to illustrate technical scheme and unrestricted, although reference
Preferred embodiment has been described in detail to the present invention, it will be understood by those within the art that, can be to the present invention's
Technical scheme is modified or equivalent, and without deviating from the spirit and scope of technical solution of the present invention, it all should be covered
In the middle of scope of the presently claimed invention.
Claims (10)
1. a kind of GM1 colon target biology adhesion tablet it is characterised in that: described biology
Adhesion tablet includes the coatings carrying tablet core and parcel described load tablet core that ratio of weight and number is 30-40: 1, described load tablet
Core is the GM1 of 3-8 part by parts by weight and the pharmaceutical carrier of 15-30 part is prepared from, institute
State coatings to be mainly prepared from by each component of following parts by weight:
2. biological adhesive tablet according to claim 1 also includes following weight portion it is characterised in that preparing described coatings
Each component of number:
Pulullan polysaccharide 2-5
Titanium dioxide 0.5-2.
3. biological adhesive tablet according to claim 1 also includes following weight portion it is characterised in that preparing described coatings
Each component of number:
Polymethyl methacrylate 3-5
D- xylose 1-2
Thioglucose 0.5-1.
4. biological adhesive tablet according to claim 1 also includes following weight portion it is characterised in that preparing described coatings
Each component of number:
Chitose 2-3
Sodium cholate 0.2-0.5.
5. biological adhesive tablet according to claim 1 also includes following weight portion it is characterised in that preparing described coatings
Each component of number:
Carbomer 0.5-1
Dithioglycollic acid 0.1-0.3
Sodium potassium tartrate tetrahydrate 0.1-0.3.
6. biological adhesive tablet according to claim 1 is it is characterised in that described pharmaceutical carrier includes following parts by weight
Each component:
7. biological adhesive tablet according to claim 6 is it is characterised in that described pharmaceutical carrier also includes following parts by weight
Each component:
Glycine 0.5-1.5
Ethylmaltol 0.2-0.5.
8. biological adhesive tablet described in a kind of claim 1 preparation method it is characterised in that: methods described comprises the steps:
S1. by GM1 and pharmaceutical carrier mix homogeneously, add appropriate 35% ethanol solution system
Standby soft material, pelletizes after 14 mesh sieves, crosses 20 mesh sieve granulate and obtain drug particles after being dried, and drug particles are placed in pressure in tablet machine
Piece can obtain load tablet core；
S2. by the 85% of ethyl cellulose, zein, dibutyl phthalate, stevioside and Mannitol 2 times of quality of addition
Mix homogeneously in ethanol water, makes coating solution；
S3. put into carrying tablet core in fluidized-bed coating machine, just film-making can be obtained using coating solution coating 20-30min, then
First film-making is placed in aging 24-48h in 45 DEG C of baking ovens and can obtain biological adhesive tablet.
9. preparation method according to claim 8 it is characterised in that: the coating parameter of described fluidized-bed coating machine is: thing
43-45 DEG C of material temperature degree, inlet temperature 60-65 DEG C, rotation speed of fan 28-30hz, atomizing pressure 0.18-0.2mpa, preheating time 5-
10min.
10. application in preparation treatment Parkinsonian drugs for the biological adhesive tablet described in any one of claim 1-9.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108815131A (en) * | 2018-09-11 | 2018-11-16 | 四川奇格曼药业有限公司 | A kind of gangliosides sustained release tablets and preparation method thereof |
| CN109288114A (en) * | 2018-10-08 | 2019-02-01 | 厦门艾赛生物科技有限公司 | Application and the sialic acid electronic cigarette liquid of a kind of sialic acid and its derivative |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1517094A (en) * | 2003-01-13 | 2004-08-04 | 重庆富进生物医药有限公司 | Monosialic acid tetrahexose ganglioside liposome complex preparation |
| CN1939315A (en) * | 2005-09-28 | 2007-04-04 | 北京赛生药业有限公司 | Ganglioside solid lipid nano-particle of monosialic acid tetrahexose and its preparation |
| CN104490837A (en) * | 2014-12-30 | 2015-04-08 | 哈尔滨医科大学科技开发总公司 | Oral preparation of monosialotetrahexosyl ganglioside sodium |
-
2016
- 2016-10-14 CN CN201610894245.2A patent/CN106361718B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1517094A (en) * | 2003-01-13 | 2004-08-04 | 重庆富进生物医药有限公司 | Monosialic acid tetrahexose ganglioside liposome complex preparation |
| CN1939315A (en) * | 2005-09-28 | 2007-04-04 | 北京赛生药业有限公司 | Ganglioside solid lipid nano-particle of monosialic acid tetrahexose and its preparation |
| CN104490837A (en) * | 2014-12-30 | 2015-04-08 | 哈尔滨医科大学科技开发总公司 | Oral preparation of monosialotetrahexosyl ganglioside sodium |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108815131A (en) * | 2018-09-11 | 2018-11-16 | 四川奇格曼药业有限公司 | A kind of gangliosides sustained release tablets and preparation method thereof |
| CN108815131B (en) * | 2018-09-11 | 2021-01-01 | 四川奇格曼药业有限公司 | Ganglioside sustained release tablet and preparation method thereof |
| CN109288114A (en) * | 2018-10-08 | 2019-02-01 | 厦门艾赛生物科技有限公司 | Application and the sialic acid electronic cigarette liquid of a kind of sialic acid and its derivative |
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| CN106361718B (en) | 2019-01-25 |
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