CN104288175A - Novel benzimidazole isomer preparation and preparation method thereof - Google Patents
Novel benzimidazole isomer preparation and preparation method thereof Download PDFInfo
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- CN104288175A CN104288175A CN201410473697.4A CN201410473697A CN104288175A CN 104288175 A CN104288175 A CN 104288175A CN 201410473697 A CN201410473697 A CN 201410473697A CN 104288175 A CN104288175 A CN 104288175A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K33/00—Medicinal preparations containing inorganic active ingredients
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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Abstract
The invention discloses a novel benzimidazole isomer preparation. The novel benzimidazole isomer preparation is prepared from the following components in parts by weight: 1-1.5 parts of omeprazole, 1-1.5 parts of berberine hydrochloride, 50-60 parts of sodium bicarbonate, 45-50 parts of magnesium hydrate, 2-3 parts of oligoester beta-cyclodextrin, 20-30 parts of oleic acid and 80-95 parts of injection water. The invention also discloses a preparation method of the novel benzimidazole isomer preparation. Omeprazole and berberine hydrochloride disclosed by the invention have synergistic effects; and the berberine hydrochloride not only can prompt the omeprazole to restrain gastric acid secretion and increase effect, but also effectively reduces the adverse effects rate. The oligoester beta-cyclodextrin is also introduced into the novel benzimidazole isomer preparation, so that the effective ingredients omeprazole and berberine hydrochloride are coated by the oligoester beta-cyclodextrin; the water solubility is effectively improved; the oligoester beta-cyclodextrin is mixed into oleinic acid, so that emulsification of the oligoester beta-cyclodextrin is also further prompted; the conditions of uneven distribution such as suspension or sedimentation are prevented; and the curative effect is greatly improved.
Description
technical field
The present invention relates to a kind of new benzimidazole isomer preparation, be specifically related to a kind of novel formulation containing omeprazole.Belong to medical art.
Background technology
Omeprazole; chemical name is 5-methoxyl group-2-{ [(4-methoxyl group-3; 5-dimethyl-2-pyridine radicals)-methyl]-sulfinyl }-1H-benzimidazole; be a kind of can the proton pump inhibitor of effective gastric acid secretion inhibiting; optionally act on gastric mucosa parietal cell; suppress to be in the activity of the H+-K+-ATP enzyme on secreted microtubule and intracytoplasmic tubular foam that parietal cell top film forms; thus the secretion of gastric acid inhibitory effectively; onset is rapid; be applicable to gastric and duodenal ulcers, reflux esophagitis and gastrinoma.Due to H
+, K
+-ATP enzyme is last process that parietal cell secretes acid, therefore this product acid suppression ability is powerful, has the effect of strong and lasting suppression basis gastric acid and food, gastric acid secretion caused by pentapeptide gastric acid secretin.It can not only the gastric acid secretion that causes of Noncompetition inhibition gastrin, histamine, choline and food, vagus nerve stimulation etc., and can suppress not by the part basis gastric acid secretion that choline or H2 receptor blocking agent affect, stimulate the gastric acid secretion caused also to have strong and lasting inhibitory action to bisfentidine is untamed by dibutyl cyclic adenosine monophosphate (DcAMP).
But omeprazole has certain side effect to digestive system, nervous system, urinary system etc., this may be reduce owing to taking Acidity in the stomach after omeprazole, is suitable for bacterial reproduction.Wherein, modal untoward reaction is diarrhoea, has a headache, feels sick.And omeprazole character is special, poorly water-soluble, be difficult to effectively be transported in diseased region or cell, its aqueous solution is unstable, and decomposes very soon in acid condition, and bioavailability is low.
Summary of the invention
The object of the invention is for overcoming above-mentioned the deficiencies in the prior art, a kind of new benzimidazole isomer preparation is provided.
For achieving the above object, the present invention adopts following technical proposals:
A kind of new benzimidazole isomer preparation, it is be made up of the component of following weight portion: omeprazole 1 ~ 1.5 part, berberine hydrochloride 1 ~ 1.5 part, sodium bicarbonate 50 ~ 60 parts, 45 ~ 50 parts, magnesium hydroxide, oligomeric esters beta-schardinger dextrin-2 ~ 3 parts, oleic acid 20 ~ 30 parts, water for injection 80 ~ 95 parts.
Preferably, be made up of the component of following weight portion: omeprazole 1 ~ 1.3 part, berberine hydrochloride 1 ~ 1.2 part, sodium bicarbonate 55 ~ 58 parts, 46 ~ 48 parts, magnesium hydroxide, oligomeric esters beta-schardinger dextrin-2 ~ 2.5 parts, oleic acid 21 ~ 25 parts, water for injection 90 ~ 95 parts.
Preferred further, be made up of the component of following weight portion: omeprazole 1.2 parts, berberine hydrochloride 1.2 parts, sodium bicarbonate 55 parts, 46 parts, magnesium hydroxide, oligomeric esters beta-schardinger dextrin-2 parts, oleic acid 25 parts, water for injection 90 parts.
Described oligomeric esters beta-schardinger dextrin-is hydroxy propyl-Beta cyclodextrin, and its substitution value is 4 ~ 5.
Above-mentioned a kind of new benzimidazole isomer preparation is freeze-dried powder.
The preparation method of described freeze-dried powder, comprises the following steps:
(1) omeprazole of recipe quantity, berberine hydrochloride, magnesium hydroxide are ground, for subsequent use;
(2) take the sodium bicarbonate of recipe quantity, be dissolved in water for injection, stir and make it dissolve;
(3) in the clear liquor of step (2), add the powder of step (1), stir 30 ~ 40 minutes, form suspension;
(4) add oligomeric esters beta-schardinger dextrin-, and slowly drip oleic acid, after dropwising, stir 20 ~ 30 minutes;
(5) adding sodium hydroxide solution adjust ph is 11.0, and adds active carbon stirring 30 ~ 40 minutes;
(6) filtering active carbon, medicinal liquid through filtering with microporous membrane, fill, lyophilization and get final product.
In described step (4), oligomeric esters beta-schardinger dextrin-is hydroxy propyl-Beta cyclodextrin, and its substitution value is 4 ~ 5.
In described step (5), the concentration of sodium hydroxide solution is 0.1mol/L.
In described step (6), microporous filter membrane is of a size of 0.22 μm.
In described step (6), freezing dry process is: be cooled to-40 DEG C, is incubated 1 hour, is slowly warming up to-5 ~ 0 DEG C of sublimation drying, then is warming up to 35 DEG C, is incubated 4 hours.
The invention has the beneficial effects as follows, the present invention is on the basis utilizing omeprazole gastric acid secretion inhibiting, make it and berberine hydrochloride combined effect, berberine hydrochloride is used to treat intestinal infection and bacillary dysentery etc. clinically, but omeprazole and berberine hydrochloride have synergism, the latter not only can impel the former to play gastric acid secretion inhibiting, plays potentiation, also effectively reduces its adverse reaction rate.Present invention further introduces oligomeric esters beta-schardinger dextrin-, make effective ingredient omeprazole and berberine hydrochloride by its enclose, effectively improve its water solublity, be mixed in oleic acid, also its emulsifying is promoted further, prevent the situation of suspension or sedimentation equal distribution inequality, its curative effect is improved largely.
Detailed description of the invention
Below in conjunction with embodiment, the present invention will be further elaborated, should be noted that following explanation is only to explain the present invention, not limiting its content.
Embodiment 1:
A freeze-dried powder containing omeprazole, be made up of following raw material:
Omeprazole 10g, berberine hydrochloride 10g, sodium bicarbonate 500g, magnesium hydroxide 450g, hydroxy propyl-Beta cyclodextrin (substitution value is 4 ~ 5) 20g, oleic acid 200g, water for injection 950g.
The preparation method of the above-mentioned freeze-dried powder containing omeprazole, comprises the following steps:
(1) omeprazole of recipe quantity, berberine hydrochloride, magnesium hydroxide are ground, for subsequent use;
(2) take the sodium bicarbonate of recipe quantity, be dissolved in water for injection, stir and make it dissolve;
(3) in the clear liquor of step (2), add the powder of step (1), stir 30 minutes, form suspension;
(4) add hydroxy propyl-Beta cyclodextrin (substitution value is 4 ~ 5), and slowly drip oleic acid, after dropwising, stir 20 minutes;
(5) adding 0.1mol/L sodium hydroxide solution adjust ph is 11.0, and adds active carbon and stir 30 minutes;
(6) filtering active carbon, medicinal liquid is through 0.22 μm of filtering with microporous membrane, and fill 500 bottles under 100 grades of environment, sends into freezer dryer, be cooled to-40 DEG C, be incubated 1 hour, be slowly warming up to-5 DEG C of sublimation dryings, then be warming up to 35 DEG C, be incubated 4 hours, obtain final product.
Embodiment 2:
A freeze-dried powder containing omeprazole, be made up of following raw material:
Omeprazole 15g, berberine hydrochloride 15g, sodium bicarbonate 600g, magnesium hydroxide 500g, hydroxy propyl-Beta cyclodextrin (substitution value is 4 ~ 5) 30g, oleic acid 300g, water for injection 950g.
The preparation method of the above-mentioned freeze-dried powder containing omeprazole, comprises the following steps:
(1) omeprazole of recipe quantity, berberine hydrochloride, magnesium hydroxide are ground, for subsequent use;
(2) take the sodium bicarbonate of recipe quantity, be dissolved in water for injection, stir and make it dissolve;
(3) in the clear liquor of step (2), add the powder of step (1), stir 40 minutes, form suspension;
(4) add hydroxy propyl-Beta cyclodextrin (substitution value is 4 ~ 5), and slowly drip oleic acid, after dropwising, stir 30 minutes;
(5) adding 0.1mol/L sodium hydroxide solution adjust ph is 11.0, and adds active carbon and stir 40 minutes;
(6) filtering active carbon, medicinal liquid is through 0.22 μm of filtering with microporous membrane, and fill 500 bottles under 100 grades of environment, sends into freezer dryer, be cooled to-40 DEG C, be incubated 1 hour, be slowly warming up to 0 DEG C of sublimation drying, then be warming up to 35 DEG C, be incubated 4 hours, obtain final product.
Embodiment 3:
A freeze-dried powder containing omeprazole, be made up of following raw material:
Omeprazole 13g, berberine hydrochloride 12g, sodium bicarbonate 550g, magnesium hydroxide 480g, oligomeric esters beta-schardinger dextrin-25g, oleic acid 210g, water for injection 950g.
The preparation method of the above-mentioned freeze-dried powder containing omeprazole, comprises the following steps:
(1) omeprazole of recipe quantity, berberine hydrochloride, magnesium hydroxide are ground, for subsequent use;
(2) take the sodium bicarbonate of recipe quantity, be dissolved in water for injection, stir and make it dissolve;
(3) in the clear liquor of step (2), add the powder of step (1), stir 35 minutes, form suspension;
(4) add hydroxy propyl-Beta cyclodextrin (substitution value is 4 ~ 5), and slowly drip oleic acid, after dropwising, stir 25 minutes;
(5) adding 0.1mol/L sodium hydroxide solution adjust ph is 11.0, and adds active carbon and stir 35 minutes;
(6) filtering active carbon, medicinal liquid is through 0.22 μm of filtering with microporous membrane, and fill 500 bottles under 100 grades of environment, sends into freezer dryer, be cooled to-40 DEG C, be incubated 1 hour, be slowly warming up to-5 DEG C of sublimation dryings, then be warming up to 35 DEG C, be incubated 4 hours, obtain final product.
Embodiment 4:
A freeze-dried powder containing omeprazole, be made up of following raw material:
Omeprazole 13g, berberine hydrochloride 12g, sodium bicarbonate 580g, magnesium hydroxide 460g, oligomeric esters beta-schardinger dextrin-25g, oleic acid 250g, water for injection 900g.
The preparation method of the above-mentioned freeze-dried powder containing omeprazole, comprises the following steps:
(1) omeprazole of recipe quantity, berberine hydrochloride, magnesium hydroxide are ground, for subsequent use;
(2) take the sodium bicarbonate of recipe quantity, be dissolved in water for injection, stir and make it dissolve;
(3) in the clear liquor of step (2), add the powder of step (1), stir 40 minutes, form suspension;
(4) add hydroxy propyl-Beta cyclodextrin (substitution value is 4 ~ 5), and slowly drip oleic acid, after dropwising, stir 20 minutes;
(5) adding 0.1mol/L sodium hydroxide solution adjust ph is 11.0, and adds active carbon and stir 30 minutes;
(6) filtering active carbon, medicinal liquid is through 0.22 μm of filtering with microporous membrane, and fill 500 bottles under 100 grades of environment, sends into freezer dryer, be cooled to-40 DEG C, be incubated 1 hour, be slowly warming up to 0 DEG C of sublimation drying, then be warming up to 35 DEG C, be incubated 4 hours, obtain final product.
Embodiment 5:
A freeze-dried powder containing omeprazole, be made up of following raw material:
Omeprazole 10g, berberine hydrochloride 12g, sodium bicarbonate 550g, magnesium hydroxide 480g, oligomeric esters beta-schardinger dextrin-20g, oleic acid 250g, water for injection 900g.
The preparation method of the above-mentioned freeze-dried powder containing omeprazole, comprises the following steps:
(1) omeprazole of recipe quantity, berberine hydrochloride, magnesium hydroxide are ground, for subsequent use;
(2) take the sodium bicarbonate of recipe quantity, be dissolved in water for injection, stir and make it dissolve;
(3) in the clear liquor of step (2), add the powder of step (1), stir 40 minutes, form suspension;
(4) add hydroxy propyl-Beta cyclodextrin (substitution value is 4 ~ 5), and slowly drip oleic acid, after dropwising, stir 25 minutes;
(5) adding 0.1mol/L sodium hydroxide solution adjust ph is 11.0, and adds active carbon and stir 30 minutes;
(6) filtering active carbon, medicinal liquid is through 0.22 μm of filtering with microporous membrane, and fill 500 bottles under 100 grades of environment, sends into freezer dryer, be cooled to-40 DEG C, be incubated 1 hour, be slowly warming up to-5 DEG C of sublimation dryings, then be warming up to 35 DEG C, be incubated 4 hours, obtain final product.
Embodiment 6:
A freeze-dried powder containing omeprazole, be made up of following raw material:
Omeprazole 1.2g, berberine hydrochloride 1.2g, sodium bicarbonate 55g, magnesium hydroxide 46g, oligomeric esters beta-schardinger dextrin-2g, oleic acid 25g, water for injection 90g.
The preparation method of the above-mentioned freeze-dried powder containing omeprazole, comprises the following steps:
(1) omeprazole of recipe quantity, berberine hydrochloride, magnesium hydroxide are ground, for subsequent use;
(2) take the sodium bicarbonate of recipe quantity, be dissolved in water for injection, stir and make it dissolve;
(3) in the clear liquor of step (2), add the powder of step (1), stir 30 minutes, form suspension;
(4) add hydroxy propyl-Beta cyclodextrin (substitution value is 4 ~ 5), and slowly drip oleic acid, after dropwising, stir 30 minutes;
(5) adding 0.1mol/L sodium hydroxide solution adjust ph is 11.0, and adds active carbon and stir 30 minutes;
(6) filtering active carbon, medicinal liquid is through 0.22 μm of filtering with microporous membrane, and fill 500 bottles under 100 grades of environment, sends into freezer dryer, be cooled to-40 DEG C, be incubated 1 hour, be slowly warming up to 0 DEG C of sublimation drying, then be warming up to 35 DEG C, be incubated 4 hours, obtain final product.
test example
Stomach or optimum activeness ulcers 140 example of duodenum is confirmed as, each 70 examples of men and women, 40 ± 5 years old mean age through gastroscopy.Be divided into 7 groups at random, adopt the method for intravenous drip, the freeze-dried powder obtained by embodiment 1 ~ 6 respectively and commercially available freeze-dried powder (be purchased from the beneficial Pharmaceuticals Ltd of Hubei DS, specification is 40mg × 10/box), treat.Intravenous drip concrete grammar is: be dissolved in by the content in bottle in 100 milliliter of 0.9% sodium chloride injection or 100 milliliter of 5% glucose injection before use, and dissolving the posterior vein instillation time should at 20 ~ 30 minute or longer.
Gastroscope is checked: recovery from illness: ulcer and around inflammation all disappear after 4 weeks; Effective: ulcer disappears but still has inflammation; Effective: ulcer reduces > more than 50%; Invalid: ulcer reduces < 50% or unchanged.
1, the healing state of ulcer compares
The healing state of table 1 ulcer compares
| Curative effect | Embodiment 1(n=20, %) | Embodiment 2(n=20, %) | Embodiment 3(n=20, %) | Embodiment 4(n=20, %) | Embodiment 5(n=20, %) | Embodiment 6(n=20, %) | Commercially available product (n=20, %) |
| Healing | 18 | 19 | 19 | 19 | 19 | 20 | 16 |
| Effective | 2 | 1 | 1 | 1 | 1 | 0 | 2 |
| Effectively | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Invalid | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Total effective rate | 100 | 100 | 100 | 100 | 100 | 100 | 90 |
As can be seen from Table 1, the total effective rate of commercially available product is only 90%, use the total effective rate of the freeze-dried powder of embodiment 1 ~ 6 treatment stomach or duodenal ulcer to reach 100%, even in embodiment 6, healing rate reaches 100%, and freeze-dried powder effectiveness of the present invention is far superior to commercially available product.
2, pain relief situation
Table 2 pain relief situation
| The alleviation situation of pain | Embodiment 1(n=20, %) | Embodiment 2(n=20, %) | Embodiment 3(n=20, %) | Embodiment 4(n=20, %) | Embodiment 5(n=20, %) | Embodiment 6(n=20, %) | Commercially available product (n=20, %) |
| Complete incidence graph number of cases in 3 days | 19 | 19 | 18 | 19 | 19 | 20 | 16 |
| Complete incidence graph number of cases in 7 days | 1 | 1 | 2 | 1 | 1 | 0 | 2 |
As can be seen from Table 2, in commercially available product 7 days, the ratio of complete incidence graph pain is 80%, in embodiment 6 100% patient medication after can complete incidence graph pain in 3 days, embodiment 1 ~ 5 100% patient's complete incidence graph pain in 7 days, in 3 days, lenitive ratio is not 90 ~ 95% not etc.
3, adverse reaction rate
Table 3 untoward reaction
| Untoward reaction | Embodiment 1(n=20, %) | Embodiment 2(n=20, %) | Embodiment 3(n=20, %) | Embodiment 4(n=20, %) | Embodiment 5(n=20, %) | Embodiment 6(n=20, %) | Commercially available product (n=20, %) |
| Diarrhoea | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Headache | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Feel sick | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
From table 3, no matter commercially available product is diarrhoea, has a headache or feel sick, and these untoward reaction all have generation, and any untoward reaction does not occur embodiment 1 ~ 6, and safety is high.
Although above-mentioned, the specific embodiment of the present invention is described; but not limiting the scope of the invention; on the basis of technical scheme of the present invention, those skilled in the art do not need to pay various amendment or distortion that creative work can make still within protection scope of the present invention.
Claims (10)
1. a new benzimidazole isomer preparation, it is characterized in that, it is be made up of the component of following weight portion: omeprazole 1 ~ 1.5 part, berberine hydrochloride 1 ~ 1.5 part, sodium bicarbonate 50 ~ 60 parts, 45 ~ 50 parts, magnesium hydroxide, oligomeric esters beta-schardinger dextrin-2 ~ 3 parts, oleic acid 20 ~ 30 parts, water for injection 80 ~ 95 parts.
2. a kind of new benzimidazole isomer preparation according to claim 1, it is characterized in that, it is be made up of the component of following weight portion: omeprazole 1 ~ 1.3 part, berberine hydrochloride 1 ~ 1.2 part, sodium bicarbonate 55 ~ 58 parts, 46 ~ 48 parts, magnesium hydroxide, oligomeric esters beta-schardinger dextrin-2 ~ 2.5 parts, oleic acid 21 ~ 25 parts, water for injection 90 ~ 95 parts.
3. a kind of new benzimidazole isomer preparation according to claim 1, it is characterized in that, it is be made up of the component of following weight portion: omeprazole 1.2 parts, berberine hydrochloride 1.2 parts, sodium bicarbonate 55 parts, 46 parts, magnesium hydroxide, oligomeric esters beta-schardinger dextrin-2 parts, oleic acid 25 parts, water for injection 90 parts.
4. a kind of new benzimidazole isomer preparation according to claim 1, it is characterized in that, described oligomeric esters beta-schardinger dextrin-is hydroxy propyl-Beta cyclodextrin, and its substitution value is 4 ~ 5.
5. a kind of new benzimidazole isomer preparation according to claim 1, is characterized in that, described new benzimidazole isomer preparation is freeze-dried powder.
6. the preparation method of a kind of new benzimidazole isomer preparation according to claim 5, is characterized in that, comprise the following steps:
(1) omeprazole of recipe quantity, berberine hydrochloride, magnesium hydroxide are ground, for subsequent use;
(2) take the sodium bicarbonate of recipe quantity, be dissolved in water for injection, stir and make it dissolve;
(3) in the clear liquor of step (2), add the powder of step (1), stir 30 ~ 40 minutes, form suspension;
(4) add oligomeric esters beta-schardinger dextrin-, and slowly drip oleic acid, after dropwising, stir 20 ~ 30 minutes;
(5) adding sodium hydroxide solution adjust ph is 11.0, and adds active carbon stirring 30 ~ 40 minutes;
(6) filtering active carbon, medicinal liquid through filtering with microporous membrane, fill, lyophilization and get final product.
7. preparation method according to claim 6, is characterized in that, in described step (4), oligomeric esters beta-schardinger dextrin-is hydroxy propyl-Beta cyclodextrin, and its substitution value is 4 ~ 5.
8. preparation method according to claim 6, is characterized in that, in described step (5), the concentration of sodium hydroxide solution is 0.1mol/L.
9. preparation method according to claim 6, is characterized in that, in described step (6), microporous filter membrane is of a size of 0.22 μm.
10. preparation method according to claim 6, is characterized in that, in described step (6), freezing dry process is: be cooled to-40 DEG C, is incubated 1 hour, is slowly warming up to-5 ~ 0 DEG C of sublimation drying, then is warming up to 35 DEG C, is incubated 4 hours.
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| CN107595845A (en) * | 2017-10-14 | 2018-01-19 | 南京正宽医药科技有限公司 | A kind of omeprazole enteric-coated capsules of gastric acid secretion inhibiting |
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