Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Oral solid preparation and application thereof

A technology of solid preparation and disintegrant, which is applied in the field of pharmaceutical preparations to achieve the effects of improving dissolution rate and improving bioavailability

Active Publication Date: 2018-02-06
WUHAN LL SCI & TECH DEV
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The oral solid preparation of the present invention disintegrates rapidly, improves its dissolution rate, thereby improving bioavailability, and can especially solve the problem of using conventional disintegrants for active substances (active ingredients) that are highly hygroscopic and will become viscous after absorbing moisture. The problem of not being able to disintegrate effectively

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Oral solid preparation and application thereof
  • Oral solid preparation and application thereof
  • Oral solid preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0107] Embodiment 1: the preparation of formula (A) compound

[0108] Dissolve the compound of formula (B) (1.0g) in dichloromethane (5ml), stir at room temperature to form a solution, add potassium phthalimide (0.27g) to the solution, keep the reaction for 4h, cool to -50 °C, filtered, and the solvent was spin-dried to obtain a solid that was the compound of formula (A) (amorphous).

[0109] Melting point: 135-145°C.

[0110] MS / HRMS m / z: 717[M+H] + ;677[M-K] - .

[0111] 1 H-NMR (400MHz, DMSO-d 6 )δ: 1.44(t, 3H), 1.46(t, 3H), 2.38(s, 3H), 2.41(s, 3H), 2.44(s, 3H), 4.64(q, 2H), 5.29(d, 1H ), 5.32(d, 1H), 5.52(d, 1H), 5.56(d, 1H), 6.86(q, 1H), 6.90(d, 2H), 7.18(m, 2H), 7.22(d, 2H) , 7.33 (m, 1H), 7.36 (m, 1H), 7.46 (d, 1H), 7.52 (dd, 1H), 7.75 (d, 1H).

[0112] 1 H-NMR spectrum and X-ray powder diffraction spectrum are shown in Figure 5 and Figure 6 .

Embodiment 2

[0113] Embodiment 2: Antihypertensive efficacy test of formula (A) compound on spontaneously hypertensive rats

[0114] Spontaneously hypertensive rats aged 12 weeks (hereinafter referred to as SHR, purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.) were anesthetized by intraperitoneal injection of 2.5% sodium pentobarbital. The blood pressure sensing catheter was inserted into the abdominal aorta, the implant was fixed on the abdominal wall, and the postoperative daily care was performed after suturing. Animals whose systolic blood pressure exceeded 160mm Hg were selected into groups, with 8 animals in each group, 3 groups in total. The matched group is given 0.5% sodium carboxymethylcellulose (hereinafter referred to as CMC-Na); formula (B) compound group and formula (A) compound group adopt 0.5% CMC-Na to dissolve, and dosage is all at 1mg / kg A Zisartan effective dose meter, the administration volume is 4mL / kg, all are administered by intragastr...

Embodiment 3

[0125] Embodiment 3: the preparation of crystal form I

[0126] (1) Take 15 mg of the compound of formula (A), add 0.2 ml of ethanol / isopropyl ether (volume ratio 1:5) mixed solution to obtain a suspension, stir at room temperature for 1 day, filter, and dry to obtain crystal form I. See the attached XRD detection pattern figure 1 ; DSC: 184°C. According to the same method, use ethanol / n-heptane (volume ratio of 1:5) mixed solution, isopropanol / n-heptane (volume ratio of 1:5) mixed solution, or tetrahydrofuran / n-heptane (volume ratio of 1:5) mixed solution was also prepared to obtain the crystal form I.

[0127] (2) Dissolve 15 mg of the compound of formula (A) in 0.1 ml of methanol to obtain a clear solution, add 1.0 ml of isopropyl ether under stirring, and precipitate a solid, continue stirring, filter, and dry to obtain crystal form I. In the same way, use good solvent ethanol / antisolvent isopropyl ether, good solvent ethanol / antisolvent methyl tert-butyl ether, good so...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Melting pointaaaaaaaaaa
Login to View More

Abstract

The invention discloses an oral solid preparation. The oral solid preparation contains any one or a mixture of any two or more of a crystal form I, a crystal form II, a crystal form III and a crystalform IV of a compound shown as a formula (A): (the formula is shown in the description). The oral solid preparation disclosed by the invention rapidly disintegrates, the dissolution rate of the oral solid preparation is improved, and further the bioavailability is improved, and the problem that active substances (active ingredients) which are high in hygroscopicity and are viscosified after moisture absorption cannot be effectively disintegrated by adopting a general disintegrating agent can be solved especially. The invention further relates to application of the oral solid preparation in preparing an angiotensin II receptor antagonist or medicines for preventing and / or treating hypertension, chronic heart failure and diabetic nephropathy.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to an oral solid preparation and its application. Background technique [0002] In general, the absorption rate of oral solid preparations depends on the dissolution (release) speed of the active substance (active ingredient) from the solid preparation, and the dissolution (release) speed of the active ingredient often depends on the disintegration speed of the solid preparation, so basically It can be considered that the disintegration rate of the oral solid dosage form is the determining step for the absorption rate of the active ingredient by the body. Most disintegrants have good water absorption and swelling properties. The role of disintegrants in oral solid preparations is to eliminate or destroy the bonding force caused by adhesives or high compression, so that they can be rapidly broken in the dissolution medium. into fine granular substances, so that the active ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K9/20A61K31/497C07D413/14A61K47/26A61K47/38A61K47/12A61K47/02A61P9/12A61P9/04A61P13/12A61P3/10
CPCA61K9/2009A61K9/2013A61K9/2018A61K9/2054A61K31/497C07D413/14C07B2200/13A61K31/42A61K31/45A61K31/501A61P9/00A61P9/12A61K9/0053
Inventor 梁雷陈永凯胡柳冯伟王朝东
Owner WUHAN LL SCI & TECH DEV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com