CN102764426B - Scorpion venom protein polypeptide colon-targeted preparation and preparation method thereof - Google Patents
Scorpion venom protein polypeptide colon-targeted preparation and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a scorpion venom protein polypeptide colon-targeted preparation and a preparation method thereof. Low-ester pectin is used as a main carrier and dripped into solution containing calcium ions, pellets are formed after reaction and solidification of the low-ester pectin, the pellets are soaked in polymine solution with a certain concentration and further cross-linked after being dried to form outer layers with higher hydrophobicity, and the scorpion venom protein polypeptide colon-targeted preparation is obtained after drying. After the preparation is taken orally, medicines are concentrated to release at the position of a colon, the concentration of the medicines at the position of the colon can be remarkably improved, the medicines directly contact with a focus of the colon and can be effectively prevented from being damaged by gastric acid or enzyme and the like in a stomach and a small intestine, and therapeutic effects of the medicines are made full use of.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to colon targeting preparation of a kind of scorpion venom protein polypeptide and preparation method thereof.More precisely, the present invention relates to a kind of can release scorpion venom to colon position and be detained micropill of long period and preparation method thereof at colon position by targeting.
Background technology
Scorpion venom is mainly comprised of protein and nonprotein two parts, and the main active of scorpion venom is protein, and reactive protein is divided into again toxic protein (charybdotoxin) and enzyme by effect difference.Charybdotoxin (Scor-pionvenom) is the toxic protein that contains the elements such as C, H, O, N, S that a class is comprised of 20～80 aminoacid, toxin has very high specificity, sulfur content is high, and molecular weight, between 6000～9000, but also has 3000 left and right or is greater than 10000.In the molecular structure of charybdotoxin, contain 3～4 pairs of disulfide bond, wherein three pairs form ringlike core structures, significant for keeping stability, performance neurotoxicity.Enzyme partly mainly contains Phospholipase A2, acetylcholine esterase, hyaluronidase etc.In scorpion venom, nonprotein composition mainly contains lipid, organic acid, multiple free amino acid, histamine, 5-hydroxytryptamine (5-HT) etc.
Scorpion venom all has pharmacological action widely to people's nervous system, cardiovascular system and energy metabolism, and the disease of the serious harm human healths such as tumor, thrombosis, pain is had to special efficacy.Lot of experiments shows: scorpion venom all has good curative effect to multiple acute and chronic pain such as Encelialgia, somatalgia, cancerous protuberance pain.The analgesic activity of scorpion venom active component is better than morphine, again without addiction, is its particular advantages.Therefore boundless in the application prospect of the aspects such as heart disease, apoplexy, cancer, colitis.
But because scorpion venom belongs to polypeptides matter, with common oral formulations, oral rear easily by the acid in stomach and small intestinal, enzyme hydrolysis, destruction, active function is lost substantially, and therapeutic effect is unsatisfactory.Conventionally adopt clinically at present the form administration of injection.But patient needs to accept acupuncture injection in medication process, and medication is painful, easily cause local muscle injury, so the compliance of patient infusion administration is poor.
Oral colon-target drug-supplying system is to make after medicine oral administration by different agent technology, at Stomach duodenum, jejunum, ileum front end, do not discharge, medicine is transported and endeavours to discharge and a kind of novel site-specific delivery of drugs system of performance part or whole body therapeutic effect after ileocecus.This system can make medicine avoid the effect of gastro-intestinal Fluid, and exactly drug conveying is discharged to colon position and slowly, not only can make medicine directly discharge at diseased region, increase local drug concentration, improve the therapeutic effect of the local large intestine diseases such as constipation, irritable bowel syndrome, ulcerative colitis, hemorrhagic colitis, Crohn`s disease, colon cancer, but also can the slow release at colon by medicine, bring into play its long-acting.Simultaneously, because colon position has pH condition gentleness relatively, proteolytic enzyme quantity is few, vigor is low, and colon wall is to the little feature of macromolecular habit barrier effect, and also the oral absorption for polypeptide protein class medicine provides an absorption window that is conducive to produce whole body therapeutic effect.
The patent No. is that the patent documentation of 00119464.X discloses a kind of metronidazole colon-specific enteric-coated tablets preparation, and said preparation is coating on the tablet of nitroimidazoles medicine; The patent No. is that 200710029476.8 patent documentation discloses colon targeting drug administration preparation of a kind of myocardium protein polypeptide and preparation method thereof, and said preparation is that the pastille micropill that adopts segmented intestine targeted coating solution to make the spice that contains myocardium protein polypeptide composition carries out coating or directly pack in segmented intestine targeted capsule shells making; The patent No. is that 200710029478.7 patent documentation discloses colon targeting preparation of a kind of orgotein polypeptide and preparation method thereof, and said preparation is that the pastille micropill that adopts segmented intestine targeted coating solution to make the spice that contains orgotein polypeptide composition carries out coating or directly pack in segmented intestine targeted capsule shells making.The content of above bibliographical information and object of the present invention and method all exist basic different.
On domestic market, there is not yet the colon targeting preparation containing scorpion venom, also have no the research report of this pharmaceutical preparation, therefore developing this class medicine not only has important clinical meaning, also has wide market prospect.
Summary of the invention
The object of this invention is to provide
colon targeting preparation of a kind of scorpion venom protein polypeptide and preparation method thereof.Of the present invention
the colon targeting preparation energy of scorpion venom protein polypeptideat colon, discharge medicine, give full play to Drug therapy effect.
The object of the present invention is achieved like this, and described is a kind of
scorpion venom protein polypeptidecolon targeting preparation, for macromolecular material with containing scorpion venom protein polypeptide drugs combinations, by dripping, solidify to form after carrying pill core and obtain with polyethyleneimine: amine aqueous solution cross-linking reaction again, it is characterized in that:
Containing the inventory of scorpion venom protein polypeptide drugs combinations and macromolecular material, by weight being 1:20 ~ 1:1, the quality concentration of volume percent that macromolecular material is dissolved in the macromolecular solution that water is mixed with is 2% ~ 15%;
The consolidation liquid that solidifies use is calcium chloride water, and the quality concentration of volume percent of calcium chloride water is 1% ~ 10%;
The crosslinked fluid of cross-linking reaction is polyethyleneimine: amine aqueous solution, and the quality concentration of volume percent of polyethyleneimine: amine aqueous solution is 0.1% ~ 10%;
Wherein saidly containing scorpion venom protein polypeptide drugs combinations, consist of by weight percentage: scorpion venom 1% ~ 100%, other medicines 99% ~ 0%; Described other medicines are that one or two or more kinds of flufenamic acid, 5-aminosalicylic acid, sulfasalazine mixes;
Described macromolecular material is that one or two or more kinds of low methoxyl pectin, sodium alginate, chitosan, ethyl cellulose mixes.
The colon targeting preparation of described scorpion venom protein polypeptide, is characterized in that: the diameter of described micropill is 0.5 ~ 1.5mm, preferably 0.8 ~ 1.2mm.
The preparation method of the colon targeting preparation of described scorpion venom protein polypeptide, comprises the following steps:
1) macromolecular material of getting formula ratio is dissolved in the water; be mixed with certain density macromolecular solution; dissolving or being evenly suspended in containing scorpion venom protein polypeptide drugs combinations and form mixed liquor in macromolecular solution formula ratio; this mixed liquor is splashed in calcium chloride water with droplet-like; solidify; filter, dry, must carry pill core;
2) get and carry pill core, immerse in polyethyleneimine: amine aqueous solution, soak, filter, dry
scorpion venom protein polypeptidecolon targeting preparation.
The preparation method of the colon targeting preparation of described scorpion venom protein polypeptide, is characterized in that: containing the combination of scorpion venom protein polypeptide drugs, be 1:20 ~ 1:1 by weight with the inventory of macromolecular material; The quality concentration of volume percent that macromolecular material is dissolved in the macromolecular solution that water is mixed with is 2 % ~ 15 %.
The preparation method of the colon targeting preparation of described scorpion venom protein polypeptide, it is characterized in that: the mixed liquor described in step 1) is to carry continuously medicinal liquid with constant flow pump, the end of constant flow pump splashes in calcium chloride water with droplet-like by injection needle or orifice analog, solidify 30min, filter, in 60 ℃ of oven dry, must carry pill core.
The preparation method of the colon targeting preparation of described scorpion venom protein polypeptide, is characterized in that: containing the combination of scorpion venom protein polypeptide drugs, be 1:20 by weight with the inventory of macromolecular material; The quality concentration of volume percent of macromolecular solution is 8 %.
According to the above-mentioned problem that needs solution, designed a kind of colon targeting preparation containing scorpion venom, it obtains with polyethyleneimine: amine aqueous solution cross-linking reaction after solidifying to form year pill core for macromolecular material and containing the combination of scorpion venom protein polypeptide drugs by dripping again, and its feature is:
Containing the combination of scorpion venom protein polypeptide drugs, be 1:20 ~ 1:1 by weight with the inventory of macromolecular material, the quality concentration of volume percent of the macromolecular solution that macromolecular material dissolved water is mixed with is 2 % ~ 15%;
The consolidation liquid that solidifies use is calcium chloride water, and the quality concentration of volume percent of calcium chloride water is 1% ~ 10%;
The crosslinked fluid of cross-linking reaction is polyethyleneimine: amine aqueous solution, and the quality concentration of volume percent of polyethyleneimine: amine aqueous solution is 0.1% ~ 10%;
Wherein saidly containing scorpion venom protein polypeptide drugs combinations, consist of by weight percentage: scorpion venom 1% ~ 100%, other medicines 99% ~ 0%; Described other medicines are that one or two or more kinds of flufenamic acid, 5-aminosalicylic acid, sulfasalazine mixes; Said medicine all has certain analgesic activity, can be used for the treatment of inflammatory pain and chronic colitis, uses and reaches synergism with scorpion venom compatibility.
Described macromolecular material is that one or two or more kinds of low methoxyl pectin, sodium alginate, chitosan, ethyl cellulose mixes.
Described low methoxyl pectin refers to that esterification degree is lower than 50% pectin.Embodiments of the invention commodity low methoxyl pectin used is generally to produce the plant material from containing high-esterpectin, is commercially available prod, can be that (esterification degree is 28% to low methoxyl pectin; Sigma, import packing product), can be also the low methoxyl pectin product that Yu Ning bio tech ltd, Anhui produces.By controlled condition, adopt gentle acid or alkali treatment, high-esterpectin can be changed into low methoxyl pectin, its functional characteristic is: solidification temperature <35 ℃, rank (USA SAG) 100 ± 5, esterification degree 15%～45%, pH value (2.5% aqueous solution) 4.5～5.0.
The diameter of the pastille micropill of making is 0.5 ~ 1.5mm, and wherein preferably diameter is 0.8 ~ 1.2mm.
According to the above-mentioned Second Problem solving that needs, designed a kind of preparation method that contains the colon targeting preparation of scorpion venom, the steps include:
(1) get being dissolved in the water of appropriate macromolecular material, be mixed with certain density macromolecular solution, to dissolve in proportion or evenly suspendible is wherein containing scorpion venom protein polypeptide drug composition, with constant flow pump, carry continuously medicinal liquid, end splashes in calcium chloride water with droplet-like by injection needle, solidifies 30min, filters, in 60 ℃ of oven dry, must carry pill core.
(2) get and carry pill core, immerse in polyethyleneimine: amine aqueous solution, soak 6h, filter, in 60 ℃ of oven dry.
The inventory of above-mentioned scorpion venom protein polypeptide and macromolecular material is 1:20 ~ 1:1 by weight, preferably 1:20; The quality concentration of volume percent of macromolecular solution is 2% ~ 15%, preferably 8%.
One of above-mentioned preparation method feature: not with an organic solvent, be aqueous solution in preparation process, can effectively avoid scorpion venom protein polypeptides matter to meet organic solvent and occur precipitation, inactivation.
Two of above-mentioned preparation method feature: adopt proceed step by step curing cross-linking reaction, react with cross-linking agent again and form the stronger skin of hydrophobicity after first solidifying, strengthen the segmented intestine targeted Release Performance of preparation.One piece of paper (Surajit Das et.al in the periodical International Journal of Pharmaceutics of Europe; 385 (2010): 20-28.) disclose solidify and crosslinked method of carrying out simultaneously, be about to consolidation liquid and crosslinked fluid and mix, medicine is wherein reacted and obtained with the direct dripping of mixed liquor of carrier material.Through comparative study, designer finds pleasantly surprisedly, adopts the segmented intestine targeted Release Performance of the preparation of proceed step by step curing cross-linking reaction gained to be obviously better than the method for bibliographical information.
Beneficial effect of the present invention:
1) preparation of the present invention adopts oral administration, avoids the misery of the long-term acupuncture injection of patient, improves compliance, and administration is safer convenience also.With respect to injection, the production technology of said preparation is simpler, and production requirement is low, without the requirement by injection, refines, regulates pH value, osmotic pressure and degerming depyrogenation.
2) preparation of the present invention is that colon position discharges medicine, can make target area drug level higher than its hetero-organization, also can enter blood circulation by per rectum, effectively avoid medicine in stomach and small intestinal by destructions such as gastric acid or enzymes, give full play to the therapeutical effect of medicine.
3) preparation of the present invention has good auxiliary therapeutic action to the disease of the serious harm human healths such as tumor, thrombosis, pain, and particularly the therapeutic effect of the local large intestine disease such as irritable bowel syndrome, ulcerative colitis, hemorrhagic colitis, Crohn`s disease, colon cancer is obvious.
Accompanying drawing explanation
Fig. 1 describes to adopt PEI to be cross-linked step by step the figure of the swelling-corrosion rate of the scorpion venom colon targeting preparation crosslinked with a step in artificial gastro-intestinal Fluid;
Fig. 2 is the figure that describes the drug-eluting curve of scorpion venom colon targeting preparation in the artificial Digestive system of difference.
The specific embodiment
Below in conjunction with specific embodiment, further illustrate the present invention.Should be understood that these embodiment are only not used in and limit the scope of the invention for the present invention is described.The experimental technique of unreceipted actual conditions in the following example, conventionally according to normal condition, or the condition of advising according to manufacturer.
embodiment 1
Take scorpion venom 10g, by scorpion venom and low methoxyl pectin mass ratio, be that 1:20 precision takes low methoxyl pectin standby.Low methoxyl pectin gradation is sprinkled in purified water, dissolves the solution of making quality concentration of volume percent 8%, add scorpion venom powder, stirring and dissolving, through supersonic oscillations scumming.With No. 6 injection needles, by the mixed solution quality concentration of volume percent that to splash into the volume of slow stirring be 50mL, be 10 % CaCl
2in solution, solidify 30min, filter, in 60 ℃ of oven dry, then bead is immersed in quality concentration of volume percent 1.0 %PEI (polymine) solution, crosslinked 6h, filters, after purified water washing in 60 ℃ of oven dry.Obtain colon targeting preparation.
Take scorpion venom 5g, by scorpion venom and low methoxyl pectin mass ratio, be that 1:10 precision takes low methoxyl pectin standby.Low methoxyl pectin gradation is sprinkled in purified water, dissolves the solution of making quality concentration of volume percent 6 %, add scorpion venom powder, stirring and dissolving, through supersonic oscillations scumming.With No. 6 injection needles, by the mixed solution quality concentration of volume percent that to splash into the volume of slow stirring be 50mL, be 8 % CaCl
2in solution, solidify 30min, filter, in 60 ℃ of oven dry, then bead is immersed in quality concentration of volume percent 0.8 %PEI solution, crosslinked 6h, filters, after purified water washing in 60 ℃ of oven dry.Obtain colon targeting preparation.
embodiment 3
Take respectively scorpion venom 5g, flufenamic acid 10g(crosses 80 mesh sieves), by medicine and low methoxyl pectin mass ratio, be that 1:15 precision takes low methoxyl pectin standby.Low methoxyl pectin gradation is sprinkled in purified water, dissolves the solution of making quality concentration of volume percent 8 %, add scorpion venom and flufenamic acid, stir suspendible even, through supersonic oscillations scumming.With No. 6 injection needles, by the mixed solution quality concentration of volume percent that to splash into the volume of slow stirring be 50mL, be 10 % CaCl
2in solution, solidify 30min, filter, in 60 ℃ of oven dry, then bead is immersed in quality concentration of volume percent 1.0 %PEI solution, crosslinked 6h, filters, after purified water washing in 60 ℃ of oven dry.Obtain colon targeting preparation.
Take respectively scorpion venom 3g, 5-aminosalicylic acid 15g(crosses 80 mesh sieves), by medicine and low methoxyl pectin mass ratio, be that 1:10 precision takes low methoxyl pectin standby.Low methoxyl pectin gradation is sprinkled in purified water, dissolves the solution of making quality concentration of volume percent 8 %, add scorpion venom and 5-aminosalicylic acid, stir suspendible even, through supersonic oscillations scumming.With No. 6 injection needles, by the mixed solution quality concentration of volume percent that to splash into the volume of slow stirring be 50mL, be 10 % CaCl
2in solution, solidify 30min, filter, in 60 ℃ of oven dry, then bead is immersed in quality concentration of volume percent 1.0 %PEI solution, crosslinked 6h, filters, after purified water washing in 60 ℃ of oven dry.Obtain colon targeting preparation.
embodiment 5
Take respectively scorpion venom 5g, sulfasalazine 10g(crosses 80 mesh sieves), by medicine and low methoxyl pectin mass ratio, be that 1:15 precision takes low methoxyl pectin standby.Low methoxyl pectin gradation is sprinkled in purified water, dissolves the solution of making quality concentration of volume percent 8 %, add scorpion venom and sulfasalazine, stir suspendible even, through supersonic oscillations scumming.With No. 6 injection needles, by the mixed solution quality concentration of volume percent that to splash into the volume of slow stirring be 60mL, be 6 % CaCl
2in solution, solidify 30min, filter, in 60 ℃ of oven dry, then bead is immersed in quality concentration of volume percent 1.0 %PEI solution, crosslinked 6h, filters, after purified water washing in 60 ℃ of oven dry.Obtain colon targeting preparation.
Use the method for preparing pastille bead in above-described embodiment to make pastille bead, then by this pastille bead fill in capsule shells, fill specification be every containing scorpion venom 10-20 milligram, obtain the capsule of colon targeting preparation.
embodiment 7
Taking respectively and adopting one-step method (is 10 %CaCl by quality concentration of volume percent
2after mixing with PEI, be cured cross-linking reaction, preparation method is as list of references simultaneously) and the method for fractional steps of the embodiment of the present invention 1 (prior to quality concentration of volume percent, be 10 %CaCl
2in solidify, after dry again with PEI cross-linking reaction) each 1g of colon targeting preparation, be suspended in the test tube that simulated gastric fluid (pH=1.2 is preheated to 37 ℃ ± 0.2 ℃) is housed, test tube is placed in to water bath with thermostatic control vibration case (37 ℃ ± 0.2 ℃) vibration (100rpm) 2h; Afterwards medium is replaced with successively to artificial intestinal fluid (pH=6.8), containing the artificial colonic fluid (pH=6) of quality concentration of volume percent 2 % pectases, 3h vibrates respectively.In different time points, from test tube, take out bead, with filter paper, suck the unnecessary moisture content in bead surface and weigh.The corrosion rate of calculating bead, result as shown in Figure 1.
By Fig. 1, known, the prepared bead of one-step method, its corrosion rate is apparently higher than the made bead of the method for fractional steps, and there is obvious corrosion phenomenon containing in the colonic fluid of pectase in the former, colon targeting preparation prepared by the confirmation method of fractional steps is compared one-step method, and the state that can hold its shape better in harmonization of the stomach intestinal fluid, is difficult for discharging at this fraction medicine, can realize better segmented intestine targeted effect, and can keep the long period at colon position.
The sample that obtains in embodiment 1 is taken in right amount, be suspended in the test tube that simulated gastric fluid (pH=1.2 is preheated to 37 ℃ ± 0.2 ℃) is housed, test tube is placed in to water bath with thermostatic control vibration case (37 ℃ ± 0.2 ℃) vibration (100rpm) 2h; Afterwards medium is replaced with successively to artificial intestinal fluid (pH=6.8), containing the artificial colonic fluid (pH=6) of quality concentration of volume percent 2% pectase, 3h vibrates respectively.Timing sampling, carries out dissolution in vitro experiment during this time.Result shows: scorpion venom colon targeting preparation is slow Slow release in simulated gastric fluid 2h and simulated intestinal fluid 3h, and cumulative release amount is less than 30%; And in containing the artificial colonic fluid of pectase, discharge and accelerate, discharge completely after 2h, in artificial colonic fluid, cumulative release amount reaches more than 70%, the release curve of the scorpion venom colon targeting preparation of seeing Fig. 2 in the artificial Digestive system of difference, illustrates that bead has segmented intestine targeted effect thus.
Barium sulfate is replaced to medicine, make colon targeting preparation, carried out tracking test in five human bodies, through X-ray, check, film making is recorded result and is shown: take after said preparation, the disintegrate position of three barium sulfate spike capsules that wherein three people take is terminal ileum position, and two people take three all in the whole disintegrates of ileocecus, do not appear at the situation of transverse colon disintegrate.
embodiment 9
Select newborn SD rat, after birth, in 8～14 days, set time every day gives 60 mmHg knot Rectal distention stimulations one time, sets up chronic Encelialgia model, control rats except not all right knot proctectasia, the same rat model of other situations.Be carried out as follows experiment grouping: matched group, contrast dosage group, model scorpion venom preparation high dose group in blank group, contrast scorpion venom group, model group, the blank matched group of model, model scorpion venom preparation low dose group, model scorpion venom preparation.Rat starts through gastrointestinal administration on the 28th day, gives continuously scorpion venom targeting preparation after 14 days, adopts obliquus externus abdominis m. to discharge to assess the sensitivity of the intestinal pain sensation; And then adopt the recording method of in vitro brain sheet field potential, observe chronic Encelialgia children Mus Hippocampus CAl district field potential LTP(long-term potentiation) variation.
Result shows, the electric discharge of model children Mus obliquus externus abdominis m. obviously strengthens, and gives scorpion venom targeting preparation low dosage, middle dosage, high dose group and compares with model group rat, and under 40,60 mmHg CRD pressure, obliquus externus abdominis m. electric discharge amplitude all significantly reduces; Record in vitro Hippocampus CAl district field potential LTP and show, model children Mus significantly increases (P<0.05) than the peak value of normal young Mus, and scorpion venom preparation significantly reduces the peak value of model children Mus Hippocampus field potential LTP.Illustrate that scorpion venom colon targeting preparation has the high quick pain causing for the treatment of internal organs, the quick effect of inhibition children's Mus Encelialgia.
Claims (5)
1. the colon targeting preparation of a scorpion venom protein, for dissolving containing scorpion venom protein pharmaceutical composition or being evenly suspended in the solution of macromolecular material, form mixed liquor, then after this mixed liquor being solidify to form to year pill core by dripping, obtain with polyethyleneimine: amine aqueous solution cross-linking reaction again, it is characterized in that:
Inventory containing scorpion venom protein pharmaceutical composition and macromolecular material is 1:20～1:1 by weight, and the quality concentration of volume percent that macromolecular material is dissolved in the macromolecular solution that water is mixed with is 2%～15%;
The consolidation liquid that solidifies use is calcium chloride water, and the quality concentration of volume percent of calcium chloride water is 1%～10%;
The quality concentration of volume percent of polyethyleneimine: amine aqueous solution is 0.1%～10%;
The wherein said percentage by weight containing scorpion venom protein pharmaceutical composition consists of: scorpion venom 1%～100%, other medicines 99%～0%; Described other medicines are that one or two or more kinds of flufenamic acid, 5-aminosalicylic acid, sulfasalazine mixes;
Described macromolecular material is low methoxyl pectin.
2. the colon targeting preparation of scorpion venom protein according to claim 1, is characterized in that: the diameter of described ball core is 0.5～1.5mm.
3. the preparation method of the colon targeting preparation of scorpion venom protein claimed in claim 1, comprises the following steps:
1) macromolecular material of getting the formula ratio in claim 1 is dissolved in the water; be mixed with certain density macromolecular solution; dissolving or being evenly suspended in containing scorpion venom protein pharmaceutical composition and form mixed liquor in macromolecular solution the formula ratio in claim 1; this mixed liquor is splashed in calcium chloride water with droplet-like; solidify; filter, dry, must carry pill core;
2) get and carry a pill core, immerse in polyethyleneimine: amine aqueous solution, soak, filter, dry to obtain the colon targeting preparation of scorpion venom protein.
4. the preparation method of the colon targeting preparation of scorpion venom protein according to claim 3, it is characterized in that: the mixed liquor described in step 1) is to carry continuously medicinal liquid with constant flow pump, the end of constant flow pump splashes in calcium chloride water with droplet-like by orifice analog, solidify 30min, filter, in 60 ℃ of oven dry, must carry pill core.
5. the preparation method of the colon targeting preparation of scorpion venom protein according to claim 3, is characterized in that: the inventory containing scorpion venom protein pharmaceutical composition and macromolecular material is 1:20 by weight; The quality concentration of volume percent of macromolecular solution is 8%.
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| CN107823178B (en) * | 2017-11-13 | 2021-02-26 | 福建卫生职业技术学院 | Niflumic acid colon targeted preparation for treating irritable bowel syndrome and preparation method thereof |
| CN112546198B (en) * | 2020-12-17 | 2022-03-25 | 温州医科大学慈溪生物医药研究院 | A pharmaceutical composition for treating cerebral apoplexy and acute cerebral infarction |
| CN115572336B (en) * | 2022-10-27 | 2024-04-26 | 上海交通大学医学院 | Colon bacteria enzyme response polymer and preparation method and application thereof |
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Non-Patent Citations (2)
| Title |
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| Colon-specific delivery of resveratrol: optimization of multi-particulate calcium-pectinate carrier;S Das, KY Ng;《International journal of pharmaceutics》;20101231;第385卷;20-28 * |
| S Das, KY Ng.Colon-specific delivery of resveratrol: optimization of multi-particulate calcium-pectinate carrier.《International journal of pharmaceutics》.2010,第385卷20-28. |
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