Oral pharmaceutical composition containing teriparatide and preparation method thereof

A technology of teriparatide and its composition, which is applied in the field of oral pharmaceutical composition containing teriparatide and its preparation, can solve the problems of side effects, difficulty in exerting the effect of absorption promotion, etc., so as to improve patient compliance and increase penetration rate and the effect on bioavailability

Pending Publication Date: 2022-06-07
ICURE BNP CO LTD
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, in the case of small animals, even if a small amount of absorption enhancer is used, the effect of promoting drug absorption can be fully exhibited, but in the case of primates and humans, where the volume of gastrointestinal tract fluid is large, there are the following disadvantages : The absorption enhancer contained in the unit dosage form is diluted by the digestive juice and water present in the intestine, and it is difficult to exert a sufficient absorption-promoting effect
In addition, there is a disadvantage that an excessive amount of absorption enhancer must be administered in order to exhibit the same level of gastrointestinal tract absorption promotion effect as that of small animals, which may cause unexplained side effects in the gastrointestinal tract due to the new synthetic surfactant

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 pharmaceutical composition containing teriparatide and preparation method thereof
  • Oral pharmaceutical composition containing teriparatide and preparation method thereof
  • Oral pharmaceutical composition containing teriparatide and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Example 1 and Comparative Example: Ionic complexation of teriparatide, deoxycholic acid, deoxycholic acid derivatives and solubilizers preparation of

[0058] Teriparatide and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a solubilizer were dissolved in pure water, and then separately prepared Aqueous solutions of deoxycholic acid derivatives to prepare ionically bonded complexes. At this time, an aqueous solution of a deoxycholic acid derivative was slowly added, so that teriparatide and N, which is a deoxycholic acid derivative, were α -Deoxycholyl-L-lysinyl methyl ester (N α -deoxycholyl-L-lysyl-methylester, DCK) in a molar ratio of 1:2 or 1:4. Then, a separately prepared aqueous solution of sodium deoxycholate was slowly added while stirring the above-mentioned complex solution to prepare an ionomer complex. At this time, an aqueous solution of deoxycholic acid was slowly added so that the molar ratio of teriparatide to deoxycholic acid was 1:4 ...

experiment example 1

[0062] Experimental Example 1: Synthesis of a complex consisting of teriparatide, deoxycholic acid, a deoxycholic acid derivative and a solubilizer Confirmation of intestinal mucosal permeability

[0063] The artificial intestinal mucosal permeability evaluation system (parallel artificial membranepermeability assay, PAMPA) was used to evaluate the effective permeability (effective permeability, P e ). First, the samples of Example 1 and Comparative Examples 1 to 7 were dissolved in phosphate buffered saline (PBS, pH 6.8) to a concentration of 200 μg / mL of teriparatide, and then 200 μL were added to the PAMPA system. The supply part and the receiving part of the PAMPA system were respectively filled with 300 μL of phosphate buffered saline (PBS, pH 6.8), and then the supply part and the receiving part were combined and left at room temperature for 5 hours. Then, the solution in each well of the receiving part and the supplying part was taken out, filtered through a membra...

experiment example 2

[0078] Experimental Example 2: Permeation of a complex consisting of teriparatide, deoxycholic acid, a deoxycholic acid derivative, and a solubilizer Confirmation of the permeability of intestinal cell membranes

[0079] The apparent permeability of the complexes prepared as in Example 1 and Comparative Examples 1 to 7 was evaluated as follows with respect to the Caco-2 cell membrane, which is an intestinal cell membrane. Caco-2 cells were individually treated to a concentration of 1 x 10 in a 24-well transfer chamber (Transwell). 5 After cells / mL, cells were cultured for 14-16 days, and then the resistance across the Caco-2 cell membrane (transmembrane resistance, TEER) value was >350 Ω cm 2 The cell monolayer was used for the experiments. First, the medium in the transfer chamber was removed, and then the supply part and the receiving part were filled with HBSS, and after culturing at 37° C. for 20 minutes, the TEER value was measured again, and then the HBSS was remove...

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

No PUM Login to view more

Abstract

The present invention relates to an oral pharmaceutical composition and a preparation method therefor, the oral pharmaceutical composition comprising an ionic bond complex consisting of teriparatide, deoxycholic acid, N [alpha]-deoxycholyl-L-lysyl methyl ester (N [alpha]-deoxycholyl-L-lysyl methyl ester, DCK), and D-[alpha]-tocopherol polyethylene glycol 1000 succinate (D-[alpha]-tocopherol polyethylene glycol 1000 succinate), the ionic bond complex comprising at least one compound selected from the group consisting of N [alpha]-deoxycholyl-L-lysyl methyl ester, N [alpha]-tocopherol polyethylene glycol 1000 succinate, N [alpha]-tocopherol polyethylene glycol 1000 succinate, N [alpha]-tocopherol polyethylene glycol 1000 succinate, N [alpha]-tocopherol polyethylene glycol 1000 succinate, N [alpha]- The oral pharmaceutical composition provided by the invention can improve the intestinal mucosa permeability and oral administration bioavailability of teriparatide and improve patient compliance, and can be used for treating osteoporosis.

Description

technical field [0001] The present invention relates to an oral pharmaceutical composition comprising teriparatide and a preparation method thereof. The oral pharmaceutical composition comprises teriparatide, deoxycholic acid, N α -Deoxycholyl-L-lysinyl methyl ester (N α -deoxycholyl-L-lysyl-methylester, DCK) and D-α-tocopherol polyethylene glycol 1000 succinate (D-α-tocopherol polyethylene glycol 1000 succinate) ionic bond complex. Background technique [0002] Parathyroid hormone (PTH) is a polypeptide composed of 84 amino acids secreted by the parathyroid gland, and it is one of the main hormones that regulates the concentration of calcium ions in the blood. It performs anabolic (bone formation) and catabolic functions in bone that vary with the time and pattern of exposure to PTH. In addition, intermittent exposure to PTH promotes anabolism, leading to a reduction in osteoblast differentiation and proliferation or apoptosis. Sustained exposure to PTH promotes cataboli...

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
Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/29A61K47/54A61K47/60A61K9/20A61K47/10A61K47/14A61K47/44A61K47/26A61K9/28A61K9/48A61K9/107A61K9/113A61P19/10
CPCA61K38/29A61K47/554A61K47/541A61K47/60A61K9/0053A61K9/2013A61K9/2031A61K9/2866A61K9/4866A61K9/4858A61K9/1075A61K9/113A61P19/10A61K9/1617A61K47/22A61K47/44A61K9/2054A61K47/10A61K47/26
Inventor 崔永权张官荣李栽范姜瑞禧徐有善罗惠林
Owner ICURE BNP CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap