Oral solid preparation and use thereof
The invention discloses an oral solid preparation containing any one, or a mixture of two or more of crystalline form I, II, III, and IV of the compound represented by formula (A). The oral solid preparation of the present invention disintegrates rapidly, increasing dissolution rate thereof, thereby improving bioavailability. In particular, it is possible to solve the problem that an active material (active ingredient), which is high hygroscopic and becomes sticky after moisture absorption, can not be effectively disintegrated by conventional disintegrants. The present invention further relates to a use of the oral solid preparation in preparing an angiotensin II receptor antagonist or a use thereof in preparing medicine for preventing and/or treating hypertension, chronic heart failure and diabetic nephropathy.
1. An oral solid preparation comprising an active ingredient, a disintegrant, a disintegrant assistant, an excipient, and a lubricant, wherein the active ingredient comprises a crystalline form of the compound of formula (A):
wherein the crystalline form of the compound of formula (A) is selected from at least one from the group consisting of crystalline form I, crystalline form II, crystalline form III, and crystalline form IV,
wherein, an X-ray powder diffraction pattern of the crystalline form I comprises characteristic peaks at diffraction angles (2-Theta) of 5.3±0.2°, 8.6±0.2°, 13.3.±0.2°, 20.1.±0.2°,
an X-ray powder diffraction pattern of the crystalline form II comprises characteristic peaks at diffraction angles (2-Theta) of 4.7±0.2°, 7.3±0.2°, 9.6±0.2°, 15.2±0.0.2°, and 26.3±0.2°,
an X-ray powder diffraction pattern of the crystalline form III comprises characteristic peaks at diffraction angles (2-Theta) of 5.2±0.2°, 8.0±0.2°, 12.4±0.2°, and 13.6±0.2°, and
an X-ray powder diffraction pattern of the crystalline form IV comprises characteristic peaks at diffraction angles (2-Theta) of 7.4±0.2°, 14.7±0.2°, 16.0±0.2°, 8.4±0.2°, 22.6±0.2°, 23.2±0.2°, and 29.7±0.2°.
2. The oral solid preparation according to claim 1 , wherein, based on a total weight of the oral solid preparation, a content of the active ingredient is about 5-50% by weight, a content of the disintegrant is about 1-20% by weight, a content of the disintegrant assistant is about 0.1-35% by weight, a content of the excipient is about 20-80% by weight, a content of the lubricant is about 0.25-10% by weight, and a weight ratio of the disintegrant to the disintegrant assistant is from 10:1 to 1:10.
3. The oral solid preparation according to claim 2 , wherein the disintegrant is a hygroscopic swelling type disintegrant selected from dry starch, croscarmellose sodium, sodium carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethyl starch, methylcellulose, low degree substituted hydroxylpropyl cellulose, crospovidone, chitosan, and microcrystalline cellulose.
4. The oral solid preparation according to claim 2 , wherein the disintegrant assistant is a soluble small molecule selected from sodium chloride, glucose, fructose, xylitol, and mixtures thereof, or
a gas generating type salt selected from sodium carbonate, calcium carbonate, potassium carbonate, calcium magnesium carbonate, zinc carbonate, magnesium carbonate, ammonium carbonate, sodium glycinate carbonate, sodium sesquicarbonate, sodium hydrogencarbonate, calcium hydrogencarbonate, potassium hydrogencarbonate, ammonium hydrogencarbonate, and mixtures thereof.
5. The oral solid preparation according to claim 2 , wherein the excipient is selected from starch, lactose, mannitol, cellulose lactose, microcrystalline cellulose, calcium hydrogen phosphate, mannitol-starch complex, and mixtures thereof; and
the lubricant is selected from talcum powder, magnesium stearate, calcium stearate, colloidal silica, hydrated silica, sodium octadecyl fumarate, polyethylene glycol, sodium stearyl fumarate, glyceryl monostearate, hydrogenated vegetable oil, and mixtures thereof.
6. The oral solid preparation according to claim 2 , wherein the oral solid preparation further comprises a binder selected from starch, pregelatinized starch, dextrin, and maltodextrin, methylcellulose, carboxy methylcellulose sodium, hydroxypropylcellulose, hypromellose, ethylcellulose, microcrystalline cellulose, gelatin, gum arabic, locust gum, peach glue, polyethylene glycol, povidone, glycerol dibehenate, carbomer, polyvinyl alcohol, poly(meth)acrylic resin, sucrose, liquid glucose, maltose alcohol, corn gluten, sodium alginate, and monolaurate.
7. A method for treating hypertension, comprising administering an effective amount of the oral solid preparation according to claim 1 to a subject in need thereof.
8. The oral solid preparation according to claim 1 , wherein, based on a total weight of the oral solid preparation,
a content of the active ingredient is about 8-30% by weight, a content of the disintegrant is about 2-18% by weight, a content of the disintegrant assistant is about 0.5-30% by weight, a content of the excipient is about 30-80% by weight, a content of the lubricant is about 0.5-8% by weight, and a weight ratio of the disintegrant to the disintegrant assistant is from 8:1 to 1:8.
9. The oral solid preparation according to claim 1 , wherein, based on a total weight of the oral solid preparation,
a content of the active ingredient is about 10-20% by weight, a content of the disintegrant is about 4-15% by weight, a content of the disintegrant assistant is about 1-25% by weight, a content of the excipient is about 50-80% by weight, a content of the lubricant is about 1-5% by weight, and a weight ratio of the disintegrant to the disintegrant assistant is from 5:1 to 1:5.
10. A method for treating hypertension, chronic heart failure, diabetic nephropathy, wherein the method comprises administering the oral solid preparation according to claim 2 to a subject in need thereof.
11. A method for treating hypertension, chronic heart failure, diabetic nephropathy, wherein the method comprises administering the oral solid preparation according to claim 3 to a subject in need thereof.
12. A method for treating hypertension, chronic heart failure, diabetic nephropathy, wherein the method comprises administering the oral solid preparation according to claim 4 to a subject in need thereof.
13. A method for treating hypertension, chronic heart failure, diabetic nephropathy, wherein the method comprises administering the oral solid preparation according to claim 5 to a subject in need thereof.
14. A method for treating hypertension, chronic heart failure, diabetic nephropathy, wherein the method comprises administering the oral solid preparation according to claim 6 to a subject in need thereof.