CN101513454A - Laxative composition with improved drug delivery system - Google Patents
Laxative composition with improved drug delivery system Download PDFInfo
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- CN101513454A CN101513454A CNA2008100061832A CN200810006183A CN101513454A CN 101513454 A CN101513454 A CN 101513454A CN A2008100061832 A CNA2008100061832 A CN A2008100061832A CN 200810006183 A CN200810006183 A CN 200810006183A CN 101513454 A CN101513454 A CN 101513454A
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- FJQXCDYVZAHXNS-UHFFFAOYSA-N methadone hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 FJQXCDYVZAHXNS-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to a laxative composition, in particular to a pharmaceutical composition, which is designed into a trapezoid to selectively deliver medicaments with a composite formula to terminal small intestine and large intestine so as to improve the effect and the safety and reduce side effect. The invention provides the laxative composition, which comprises a kernel containing the medicaments, a kernel sealing layer, a pyridoxol layer which is separated from the kernel and contains pyridoxol, and a delayed release layer formed to release the medicaments to the terminal small intestine and the large intestine.
Description
Technical field
The present invention relates to anti-constipation composition, relate in particular to a kind of like this cathartic synthetic of the drug delivery system through improving, its drug selectivity ground with compound prescription is delivered to distal small intestine and large intestine, thereby improves effect and safety, and the minimizing side effect.
Background technology
Cathartic is divided into dilatancy cathartic, saline cathartic or motivator cathartic (stoolsoftner) and irritant laxative (page 1070 for Laxatives, Martindale, the research book of U.S. pharmaceuticals office).Saline cathartic has magnesium oxide, heavy-burned magnesia, magnesium hydroxide, magnesium carbonate and magnesium sulfate etc., and the dilatancy cathartic mainly is the cathartic of fiber system, for example, and sodium carboxymethyl cellulose, carboxymethylcellulose calcium, semen pulicariae (Psyllium seed) etc.The motivator cathartic is called as stool softener, and docusate sodium (Colace), soft stool agent (surfak), Pu Luoshamu (poloxalkol) and docusate sodium (Docusate sodium) etc. are arranged.Irritant laxative has diphenyl methane (diphenylmethane) derivant bisacodyl (bisacodyl) and phenolphthalein (phenolphthalein), Cotex rhamni (Cascara sagrada), Radix Et Rhizoma Rhei, Folium Sennae (SENNAE FOLIUM), Aloe (Aloe), alder buckthornalder dogwood (Rhamnus frangula) and Semen Pharbitidis etc.Outside, in order to keep equilibrium to enteral feeding vitamin and nutrition, use nicotiamide is arranged, Vitamin B1 with and derivant, Vitamin B6 and derivant thereof etc., for the health of intestinal, using has dry yeast and growth viable bacteria to become to grade.
Irritant laxative is a macromolecule, is can't digestion/absorption in small intestinal, flows to the large intestine place, and the bacterial decomposition by big enteral is converted into active substance.Active substance stimulates the large intestine inwall, promotes colon movement, thereby induces stool, still, at this moment draws stool powerfully, so when using separately, to patient's misery that arrives.Therefore, generally, irritant laxative uses with the wellability cathartic that plays softening stool and lubrication.But, even use, also can't avoid side effect such as stomachache, diarrhoea fully with the wellability cathartic, such side effect is along with the irritant laxative of taking arrives gastrointestinal position difference and its intensity difference.And, mostly be and also take pyridoxine hydrochloride (pyridoxine hydrochloride) simultaneously, so that the vitamin that reduces because of the effect of irritant laxative to enteral feeding, but interpolation pyridoxine hydrochloride, then promote the feature of the bisacodyl that the different structure along with temperature and pH changes, therefore cause the problem of the content that reduces bisacodyl.
Summary of the invention
Therefore, the object of the present invention is to provide a kind of anti-constipation composition and manufacture method thereof, the medicine of the compound formation of this anti-constipation composition by will comprising irritant laxative is by prescription (formulation) design, optionally be delivered to distal small intestine and large intestine, thereby will suffer from abdominal pain, the side effect of irritant laxative such as diarrhoea minimizes, and improves defecation speed and effect.
And, another object of the present invention is to provide a kind of anti-constipation composition, it is designed to trapezoidal, and interactional medicine is separated, thereby improves stability, and can prevent also that when long-time keeping drug effect from descending.
In addition, can clear and definite other purposes of the present invention and advantage by the following embodiment of the invention.
In order to realize above-mentioned purpose, anti-constipation composition provided by the invention comprises:
(a) kernel
It comprises the bisacodyl of 1 weight portion, the Radix Et Rhizoma Rhei extract of 4～10 weight portions, the Radix Paeoniae extraction powder of 7～10 weight portions
The calcium pantothenate of the docusate sodium of 2～5 weight portions and 1～2 weight portion (Calcium Pantothenate);
(b) kernel sealant, it comprises the water soluble polymer of 0.5～11 weight portion, it is around above-mentioned kernel;
(c) pyridoxol layer, it comprises the pyridoxine hydrochloride of 1～2 weight portion and the water soluble polymer of 0.1～2 weight portion, and around above-mentioned sealant; And
(d) postpone releasing layer (slow release layer), it comprises the enteric solubility macromolecule of 2～5 weight portions, and around above-mentioned pyridoxol layer.
And the present invention also provides the manufacture method of the anti-constipation composition that may further comprise the steps:
(a) mix the bisacodyl of 1 weight portion, the Radix Et Rhizoma Rhei extract of 4～10 weight portions, Radix Paeoniae extraction powder, the docusate sodium of 2～5 weight portions and the calcium pantothenate of 1～2 weight portion of 7～10 weight portions, play ingot, the preparation kernel;
(b) with the water soluble polymer liquid of the water soluble polymer that in the solvent of 10～60 weight portions, dissolves 0.5～11 weight portion, be coated with above-mentioned kernel, form the kernel sealant;
(c) with the liquid of the water soluble polymer of the pyridoxine hydrochloride of dissolving 1～2 weight portion in the purifying waste water of 10～40 weight portions and 0.1～2 weight portion, be coated with above-mentioned kernel sealant, form the pyridoxol layer; And
(d) with the enteric solubility macromolecule liquid of enteric solubility macromolecule dissolution in solvent, be coated with above-mentioned pyridoxol layer, form the delay releasing layer 2～5 weight portions.
" enteric solubility macromolecule (enteric polymer) " in this description be meant at pH and be the macromolecule of non-dissolubility or safety under less than 5 acid condition, pH more than or equal to 5 condition under dissolving or the macromolecule that decomposes.
" delay releasing layer " in this description is the coating layer that the release of medicine is prolonged certain hour, refers generally to the enteric solubility coating layer.
" protective layer " in this description is to prevent to postpone that releasing layer is subjected to outside stimulation and impaired, improves aesthetic property and the layer that forms, is often referred to the peeling layer or the sugarcoating layer that allow on the pharmaceutics.
" sealing (sealing) " in this description is meant that the water transport in order to prevent sugarcoating layer or thin layer seals kernel to kernel.
Anti-constipation composition of the present invention comprises the kernel that contains medicine, kernel sealant, separate and comprise the pyridoxol layer of pyridoxol with kernel, be used for discharging to distal small intestine and large intestine the delay releasing layer of medicine.Below, describe in detail respectively.
Kernel
Kernel comprises that the Radix Et Rhizoma Rhei extract of irritant laxative bisacodyl, 4～10 weight portions of 1 weight portion, the Radix Paeoniae of 7～10 weight portions extract the wellability cathartic docusate sodium of powder and 2～5 weight portions, outside also comprise the calcium pantothenate of 1～2 weight portion.And, as required, also comprise the excipient (Pharmaceutical Excipients) and the disintegrating agent that allow use on the pharmaceutics.As the representative of excipient, can use lactose etc., can use Talcum, magnesium stearate (Magnesium Stearate) etc. as disintegrating agent.Preferably, as above-mentioned excipient and disintegrating agent, above-mentioned kernel comprises the lactose of 10～15 weight portions, the Talcum of 1～2 weight portion, the magnesium stearate of 0.1～1 weight portion.By mixing above-mentioned medicine, disintegrating agent etc. can obtain this compositions afterwards by the method for playing ingot kernel.
The kernel sealant
Water soluble polymer liquid with the water soluble polymer that dissolves 0.5～11 weight portion in the solvent of 10～60 weight portions is coated with above-mentioned kernel, forms the kernel sealant.As above-mentioned water soluble polymer, preferably, use separately or mixing use hydroxypropyl emthylcellulose (HPMC), Polyethylene Glycol (polyehlyene glycol) etc.More preferably, use the hydroxypropyl emthylcellulose of 0.5～2 weight portion and the polyethylene glycol 6000 of 0.01～9 weight portion as above-mentioned water soluble polymer.As solvent, so long as allow to use on the pharmaceutics, and can dissolve the solvent of above-mentioned water soluble polymer, can use.The preferred volatilizable organic solvents such as ethanol, acetone that use are more preferably the mixed solvent that uses ethanol and acetone.In a preferred embodiment of the invention, used with 1.625: 1 blended ethanol of ratio and acetone mixed solvent.
The pyridoxol layer
The pyridoxol layer is the layer that the medicine that comprises with above-mentioned kernel separates and contain pyridoxine hydrochloride, and it is around above-mentioned kernel sealant.The mixed solution that the pyridoxine hydrochloride by dissolving 1～2 weight portion in the purifying waste water of 10～40 weight portions and the water soluble polymer of 0.1～2 weight portion obtain is coated with above-mentioned kernel sealant, forms the pyridoxol layer.At this moment, can use or mix use hydroxypropyl emthylcellulose and Polyethylene Glycol etc. separately as water soluble polymer.More preferably, as above-mentioned water soluble polymer, use the hydroxypropyl emthylcellulose of 0.1～1 weight portion and the polyethylene glycol 6000 of 0.01～1 weight portion together.
Postpone releasing layer
The delay releasing layer comprises the enteric solubility macromolecule of 2～5 weight portions, and around above-mentioned pyridoxol layer.By being coated with above-mentioned pyridoxol layer in the macromolecule liquid of solvent, the enteric solubility macromolecule dissolution forms the delay releasing layer.Can use the general enteric solubility macromolecule that uses on the pharmaceutics as above-mentioned enteric solubility macromolecule, preferably use the copolymer You Teqi (Eudragit) of methacrylic acid and methyl methacrylate
TM(the strange S100 of You Te, the strange L100 of You Te etc.).Methyl methacrylate=1: 1) and the strange L100 of the You Te of 1～2 weight portion (methacrylic acid: methyl methacrylate=1: 2) and the triethyl citrate of 0.1～1 weight portion (Triethyl Citrate) be more preferably, use the strange S100 of the You Te (methacrylic acid: of 0.1～1 weight portion as above-mentioned enteric solubility macromolecule.The ratio that is more preferably with 1: 2.4 uses strange S100 of You Te and the strange L100 of You Te.In order to make the delay releasing layer more lubricious, preferably also comprise the Talcum of 10～30 weight portions than intestinal thin film.
As solvent, as long as can use on the pharmaceutics, and can dissolve the high molecular solvent of selected enteric solubility, can use.Be preferably independent use or mix use or use volatilizable organic solvents such as ethanol, acetone with water.Be more preferably the mixed solvent that uses ethanol, acetone, purifies waste water.In a preferred embodiment of the invention, used 5: 8: 0.65 the blended acetone of ratio/purify waste water.
Protective layer
Anti-constipation composition of the present invention preferably also comprises around protective layers such as the peeling layer of above-mentioned delay releasing layer or sugarcoating layers.Can form peeling layer and sugarcoating layer by the known usual method in pharmaceutics field.Preferably, coating comprises the HPMC of 1～5 weight portion, the polyethylene glycol 6000 of 0.1～1 weight portion, the steatitic protective layer of 1～10 weight portion in the lozenge that is formed with the delay releasing layer that obtains in above-mentioned, forms the peeling layer.Perhaps preferably, being formed with in the lozenge that postpones releasing layer of above-mentioned preparation, formation comprises the white sugar of 5～10 weight portions, the arabic gum of 0.1～5 weight portion (gum arabic), the precipitated calcium carbonate of 5～20 weight portions, the sugarcoating layer of 0.01～1 parts by weight of titanium oxide.
Description of drawings
Fig. 1 is the chart that external (in vitro) slaking test result is shown;
Fig. 2 is the chart that (in vivo) clinical test results is shown in vivo.
The specific embodiment
Below, describe the present invention in detail with specific embodiment.But the present invention limits in the following embodiments, and in the scope of putting down in writing in not breaking away from technological thought of the present invention and claims, those skilled in the art can have multiple modification and distortion.
Embodiment 1-2
Make kernel
With the composition of following table 1, make kernel.
Table 1
1) at first, the polyvidone of dissolving 10.0mg and the docusate sodium of 18.0mg in ethanol/acetone (1: the 1) mixed solvent of 0.042ml;
2) in addition, the Radix Paeoniae that mixes 50mg is extracted the Radix Et Rhizoma Rhei extract of powder and 28.6mg, uses above-mentioned 1) the middle mixed solution for preparing, under the condition below, form granule and also carry out drying.
Machinery title: GPCG-1 (GLATT, Germany)
Implantation temperature: 50 ℃
Discharge temperature: 38～42 ℃
Product temperature: 40 ℃
Jet velocity: 1mL/min
3) ingot is played in mixing
Embodiment 1: with the particulate matter 2 of preparation) and the bisacodyl of 6.0mg, the calcium pantothenate of 7.0mg, the lactose of 16.4mg, the polyvinylpolypyrrolidone of 30.0mg, the Talcum of 3.5mg, the magnesium stearate mixing of 0.5mg, and play ingot.
Embodiment 2: with the particulate matter 2 of preparation) and the bisacodyl of 6.0mg, the calcium pantothenate of 7.0mg, the avicel cellulose of 16.4mg, the polyvinylpolypyrrolidone of 30.0mg, the Talcum of 3.5mg, the magnesium stearate mixing of 0.5mg, and play ingot.
Embodiment 3-4
Sealing
Composition with following table 2 seals the kernel for preparing in the foregoing description 1.
Table 2
1) embodiment 3: the hydroxypropyl methylcellulose 2910 of dissolving 5mg and the polyethylene glycol 6000 of 0.5mg in the mixed solvent of ethanol/acetone/purify waste water (3.8: 5.2: 0.5) of 0.095ml.
Embodiment 4: the polyvinyl alcohol of dissolving 5mg and the polyethylene glycol 6000 of 0.5mg in the mixed solvent of ethanol/acetone/purify waste water (3.8: 5.2: 0.5) of 0.095ml.
2) with following conditions, with above-mentioned 1) in the preparation mixed solvent be injected on the kernel of embodiment 1, finish sealing.
The machinery name: Hicoater 130
Implantation temperature: 65～70 ℃
Discharge temperature: 35～45 ℃
Air pressure: 1.5～2.0kg/cm
2
Fan speed: 4～7rpm
Jet velocity: 370mL/min
The pyridoxine hydrochloride layer
Composition with following table 3 constitutes the pyridoxine hydrochloride layer, to the kernel injection coating of the sealing for preparing at the foregoing description 3.
Table 3
1) embodiment 5: hydroxypropyl methylcellulose 2910, the pyridoxine hydrochloride of 12mg and the polyethylene glycol 6000 of 0.32mg of dissolving 3.2mg in the purifying waste water of 0.05ml.
Embodiment 6: polyvinyl alcohol, the pyridoxine hydrochloride of 12mg and the polyethylene glycol 6000 of 0.32mg of dissolving 3.2mg in the purifying waste water of 0.05ml.
2) with following conditions the kernel that seals at embodiment 3 is sprayed, finish the sealing of pyridoxine hydrochloride layer.
Machinery name: Hicoater130
Implantation temperature: 65～70 ℃
Discharge temperature: 35～45 ℃
Air pressure: 1.5～2.0kg/cm
2
Fan speed: 4～7rpm
Jet velocity: 370mL/min
Postpone the manufacturing of releasing layer
Composition with following table 4 constitutes the delay releasing layer, to the coating of spraying at the lozenge of the foregoing description 5 preparations.
Table 4
1) embodiment 7: the strange L100 of You Te of the strange S100 of You Te, the 9.5mg of dissolving 4mg, the triethyl citrate of 4mg in acetone/purify waste water (5: 8: 0.65) of 0.137ml, add the Talcum of 13.5mg again, and make its suspension.
Embodiment 8: dissolve the strange L100 of You Te of the strange S100 of You Te, the 8.5mg of 5mg, the triethyl citrate of 4mg in acetone/purify waste water (5: 8: 0.65) of 0.137ml, add the Talcum of 13.5mg again, make its suspension.
2) spray to the lozenge that is formed with the pyridoxine hydrochloride layer for preparing at embodiment 5 with following conditions, finish the delay releasing layer.
The machinery name: Hicoater 130
Implantation temperature: 40～45 ℃
Discharge temperature: 30～35 ℃
Air pressure: 1.5～2.0kg/cm
2
Fan speed: 4～7rpm
Jet velocity: 140mL/min
Embodiment 9～10
Make protective layer
Composition with following table 5 constitutes protective layer, to the coating of spraying at the lozenge of the foregoing description 7 preparations.
Table 5
Embodiment 9
1) hydroxypropyl methylcellulose 2910 of dissolving 3.2mg and the polyethylene glycol 6000 of 0.32mg in the purifying waste water of 0.05ml.
2) with following conditions, the lozenge that postpones releasing layer to the formation in embodiment 7 preparation is injected in above-mentioned 1) mixed solution of preparation, thus finish protective layer.
The machinery name: Hicoater 130
Implantation temperature: 65～70 ℃
Discharge temperature: 35～45 ℃
Air is pressed: 1.5～2.0kg/cm
2
Fan speed: 4～7rpm
Jet velocity: 370mL/min
1) gelatin of dissolving 1.84mg, the gummi arabicum pulveratum of 2.0mg, the white sugar of 35.4mg in the purifying waste water of 0.086ml.
2) with following conditions, to the lozenge that postpones releasing layer being formed with of embodiment 7 preparation add 1/10 above-mentioned 1) in the mixed solution for preparing, spill the deposition calcium carbonate of 9.146mg, the titanium dioxide of 0.015mg again, and carry out drying, repeat 10 times.
The machinery name: Hicoater 130
Implantation temperature: 65～70 ℃
Discharge temperature: 35～45 ℃
Fan speed: 4～7rpm
Comparative example 1
1) makes kernel
Composition with following table 6 is made kernel.
1. at first, the polyvidone of dissolving 10.0mg and the docusate sodium of 18.0mg in ethanol/acetone (1: the 1) mixed solvent of 0.042ml;
Table 6
| The raw material medicine | Weight (mg) |
| Bisacodyl | 6.0 |
| Docusate sodium | 18.0 |
| Radix Paeoniae is extracted powder | 50.0 |
| Radix Et Rhizoma Rhei extract | 28.6 |
| Calcium pantothenate | 7.0 |
| Pyridoxine hydrochloride | 12.0 |
| Lactose | 16.4 |
| Polyvidone | 10 |
| Polyvinylpolypyrrolidone | 30.0 |
| Talcum | 3.5 |
| Magnesium stearate | 0.5 |
| Total amount | 182.0 |
2. in addition, the Radix Paeoniae that mixes 50mg is extracted the Radix Et Rhizoma Rhei extract of powder and 28.6mg, uses above-mentioned 1) the middle mixed solution for preparing, under the condition below, form granule and also carry out drying.
Machinery title: GPCG-1 (GLATT, Germany)
Implantation temperature: 50 ℃
Discharge temperature: 38～42 ℃
Product temperature: 40 ℃
Jet velocity: 1mL/min
3. particulate matter and the bisacodyl of 6.24mg, the calcium pantothenate of 8.4mg, the pyridoxine hydrochloride of 12.0mg, the lactose of 14.76mg, the polyvinylpolypyrrolidone of 30mg, the Talcum of 3.5mg, the magnesium stearate of 0.5mg of preparation are mixed, and played ingot.
2) sealing
Composition with following table 7 is sealed in above-mentioned 1) the middle kernel for preparing.
Table 7
| The raw material medicine | Weight (mg) |
| Hydroxypropyl methylcellulose 2910 | 5 |
| Polyethylene glycol 6000 | 0.5 |
| Total amount | 5.5 |
1. the hydroxypropyl methylcellulose 2910 of dissolving 5mg and the polyethylene glycol 6000 of 0.5mg in the mixed solvent of ethanol/acetone/purify waste water (3.8: 5.2: 0.5) of 0.095ml;
2. below under the condition, to above-mentioned 1) in the kernel of preparation spray, finish sealing.
The machinery name: Hicoater 130
Implantation temperature: 65～70 ℃
Discharge temperature: 35～45 ℃
Air is pressed: 1.5～2.0kg/cm
2
Fan speed: 4～7rpm
Jet velocity: 370mL/min
3) manufacturing delay releasing layer
Finish the delay releasing layer with the composition of following table 8.
Table 8
| The raw material medicine | Weight (mg) |
| You Teqi S100 | 13.5 |
| |
4 |
| Talcum | 13.5 |
| Total amount | 31 |
1. in acetone/purify waste water (5: 8: 0.65) of 0.137ml, dissolve the strange S100 of You Te of 13.5mg, the triethyl citrate of 4mg, add the Talcum of 13.5mg afterwards again, make its suspension;
2. with following conditions, to above-mentioned 2) in the lozenge of preparation spray, finish the delay releasing layer.
The machinery name: Hicoater 130
Implantation temperature: 40～45 ℃
Discharge temperature: 30～35 ℃
Air pressure: 1.5～2.0kg/cm
2
Fan speed: 4～7rpm
Jet velocity: 140mL/min
4) make protective layer
Finish the protective layer of comparative example with the composition of following table 9.
Table 9
| The raw material medicine | Weight (mg) |
| Gelatin | 1.84 |
| Gummi arabicum pulveratum | 2.0 |
| White sugar | 35.4 |
| The deposition calcium carbonate | 91.46 |
| Titanium dioxide | 0.15 |
| Palm wax | 0.05 |
| Total amount | 130.90 |
1. gelatin, the gummi arabicum pulveratum of 2.0mg and the white sugar of 35.4mg of dissolving 1.84mg in the purifying waste water of 0.086ml;
2. with the part that cooks noodle, to above-mentioned 3) in preparation be formed with each 1/10 the 1. liquid that adds of the lozenge that postpones releasing layer, spill the titanium dioxide of winnofil, 0.015mg of 9.146mg again after, carry out drying, repeat 10 times.
The machinery name: Hicoater 130
Implantation temperature: 65～70 ℃
Discharge temperature: 35～45 ℃
Fan speed: 4～7rpm
Test example 1
External slaking test
Use the sugar-coated ingot of preparation in embodiment 10 and the comparative example 1, test according to British Pharmacopoeia (British Pharmacopoeia) slaking test method, slaking test liquid has used pH7.0 and pH8.5.Its result such as following table 10 and Fig. 1.
Carry out the result of the slaking test of embodiment 10 and comparative example 1 in ph7.0 and pH8.5, under the situation of large intestine top condition pH7.0, comparative example 1 needs 60 minutes, and embodiment 10 needs 48 minutes.And under the situation of large intestine bottom condition pH8.5, comparative example 1 needs 37 minutes, and embodiment 10 needs 25 minutes, demonstrates with comparative example 1 and compares, and the disintegration rate of embodiment 10 is faster.
Table 10
| |
Comparative example 1 | |
| pH7.0 | 48min | 60min |
| pH8.5 | 25min | 37min |
Test example 2
In the body
Clinical trial
Select 12 male and 14 women in 20-30 year, make them take the sugar-coated ingot of preparation in embodiment 10 and the comparative example 1.When selecting, got rid of diarrhoea, colitis patient, anemia of pregnant woman and taken the cathartic person, and forbidden drinking at duration of test.Between when 15-17, (medicine) being taken before meal 2 ingots are measured defecation speed and side effect frequency.Taking an after date,, withdrawing a week for taking of following first phase.Detect defecation speed with initial stool time kimonos with constantly time difference, with expand, feel sick, feel sad, the number of times of serious float downward sense of discomfort and diarrhoea etc. detects the side effect frequency.Consequently as following table 11 and Fig. 2.
The defecation time of comparative example 1 is 14.4 hours, and the defecation time of embodiment 10 is 8.3 hours, approximately fast 1.7 times of the defecation times of embodiments of the invention 10.This is consistent soon with the disintegration time among the external slaking test result.The side effect frequency is that comparative example 1 is 7 times, and embodiment 10 is 5 times, and about less about 2 times of compositions of the present invention has surpassed defecation time effect ratio.
Table 11
| |
Comparative example 1 | |
| Defecation time | 8.3 hour | 14.4 hour |
| The |
5 |
7 times |
Test example 3
Safety testing
Use the sugar-coated ingot of preparation in embodiment 10 and the comparative example 1, in 40 ℃ of relative humiditys 75%, carried out accelerated test.Following table 12 is results of the safety testing of bisacodyl and pyridoxine hydrochloride.
Table 12
Can know that from above-mentioned result of the test in the comparative example 1, because reacting to each other between pyridoxine hydrochloride and the bisacodyl, the content of bisacodyl descends.This point can change Form because of pyridoxine hydrochloride according to bisacodyl, reduces safety and judges.But, among the embodiment 10 that after two kinds of compositions are separated fully, is coated with, be independent of each other mutually, keep stable status.
Commercial Application
The present invention will for the drug selectivity of the compound prescription of cathartic be delivered to distal small intestine and large intestine, thereby irritant laxative stimulated intestinal mucosa and the stomachache that occurs, the minimized effect that improves simultaneously cathartic of side effect such as feel cold, shake, but the pyridine of pyrrole sand separates with kernel fully with puridoxine hydrochloride, prevent from interacting, thereby but improved the security of pyrrole sand pyridine. Anti-constipation composition of the present invention can significantly improve the utilization rate because of the at present limited irritant laxative of side effect.
Claims (14)
1. anti-constipation composition comprises:
(a) kernel, described kernel comprise the bisacodyl of 1 weight portion, the Radix Et Rhizoma Rhei extract of 4～10 weight portions, Radix Paeoniae extraction powder, the docusate sodium of 2～5 weight portions and the calcium pantothenate of 1～2 weight portion of 7～10 weight portions;
(b) kernel sealant, it comprises the water soluble polymer of 0.5～11 weight portion, and around described kernel;
(c) pyridoxol layer, it comprises the pyridoxine hydrochloride of 1～2 weight portion and the water soluble polymer of 0.1～2 weight portion, and around described sealant; And
(d) postpone releasing layer, it comprises the enteric solubility macromolecule of 2～5 weight portions, and around described pyridoxol layer.
2. anti-constipation composition according to claim 1 is characterized in that:
The water soluble polymer that forms described pyridoxol layer comprises the hydroxypropyl emthylcellulose of 0.1～1 weight portion and the polyethylene glycol 6000 of 0.01～1 weight portion.
3. anti-constipation composition according to claim 2 is characterized in that:
The water soluble polymer that forms described kernel sealant comprises the hydroxypropyl emthylcellulose (HPMC) of 0.5～2 weight portion and the polyethylene glycol 6000 of 0.01～9 weight portion.
4. anti-constipation composition according to claim 3 is characterized in that:
The strange S100 of You Te that described enteric solubility macromolecule comprises 0.1～1 weight portion, the strange L100 of You Te of 1～2 weight portion and the triethyl citrate of 0.1～1 weight portion.
5. anti-constipation composition according to claim 4 is characterized in that:
Described delay releasing layer also comprises the Talcum of 10～30 weight portions.
6. anti-constipation composition according to claim 5 is characterized in that:
Described kernel also comprises the lactose of 10～15 weight portions, the Talcum of 1～2 weight portion and the magnesium stearate of 0.1～1 weight portion.
7. according to each described anti-constipation composition of claim 1 to 6, it is characterized in that also comprising:
Peeling layer or sugarcoating layer around described delay releasing layer.
8. the manufacture method of an anti-constipation composition may further comprise the steps:
(a) bisacodyl of 1 weight portion, the Radix Et Rhizoma Rhei extract of 4～10 weight portions, the Radix Paeoniae extraction powder of 7～10 weight portions, the docusate sodium of 2～5 weight portions and the calcium pantothenate of 1～2 weight portion are mixed, play ingot, the preparation kernel;
(b) with the water soluble polymer liquid of the water soluble polymer that in the solvent of 10～60 weight portions, dissolves 0.5～11 weight portion, be coated with described kernel, form the kernel sealant;
(c) with the liquid of the water soluble polymer of the pyridoxine hydrochloride of dissolving 1～2 weight portion in the purifying waste water of 10～40 weight portions and 0.1～2 weight portion, be coated with described kernel sealant, form the pyridoxol layer; And
(d) with the enteric solubility macromolecule liquid of enteric solubility macromolecule dissolution in solvent, be coated with described pyridoxol layer, form the delay releasing layer 2～5 weight portions.
9. the manufacture method of anti-constipation composition according to claim 8, it is characterized in that: the water soluble polymer that forms described pyridoxol layer comprises the hydroxypropyl emthylcellulose of 0.1～1 weight portion and the polyethylene glycol 6000 of 0.01～1 weight portion.
10. the manufacture method of anti-constipation composition according to claim 9, it is characterized in that: the water soluble polymer that forms described kernel sealant comprises the hydroxypropyl emthylcellulose HPMC of 0.5～2 weight portion and the polyethylene glycol 6000 of 0.01～9 weight portion.
11. the manufacture method of anti-constipation composition according to claim 10 is characterized in that: the strange S100 of You Te that described enteric solubility macromolecule comprises 0.1～1 weight portion, the strange L100 of You Te of 1～2 weight portion and the triethyl citrate of 0.1～1 weight portion.
12. the manufacture method of anti-constipation composition according to claim 11 is characterized in that:
The step of described preparation kernel also comprises mixes the magnesium stearate of the Talcum of the lactose of 10～15 weight portions, 1～2 weight portion and 0.1～1 weight portion, and plays ingot.
13. the manufacture method of anti-constipation composition according to claim 12 is characterized in that:
Described enteric solubility macromolecule liquid also comprises the Talcum of 10～30 weight portions.
14. the manufacture method of each described anti-constipation composition in 13 is characterized in that according to Claim 8, also comprises:
On the anti-constipation composition that is formed with described delay releasing layer, form peeling layer or sugarcoating layer.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100061832A CN101513454A (en) | 2008-02-21 | 2008-02-21 | Laxative composition with improved drug delivery system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100061832A CN101513454A (en) | 2008-02-21 | 2008-02-21 | Laxative composition with improved drug delivery system |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101513454A true CN101513454A (en) | 2009-08-26 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008100061832A Pending CN101513454A (en) | 2008-02-21 | 2008-02-21 | Laxative composition with improved drug delivery system |
Country Status (1)
| Country | Link |
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2008
- 2008-02-21 CN CNA2008100061832A patent/CN101513454A/en active Pending
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Open date: 20090826 |