Formula of oral mucosa absorbing dosage form of medicines of polypeptides and proteins, and preparation method and application thereof

A technology of oral mucosa and absorbents, which is applied in the formulation, preparation and application of oral mucosa absorption dosage forms of polypeptide and protein drugs, and can solve the problems of difficult curative effect of polypeptide and protein drugs, short action time of chewing gum, and patch The problem of limited drug loading can achieve the effect of improving bioavailability, avoiding drug loss, and simplifying the composition of the prescription

Inactive Publication Date: 2010-09-29
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Nitroglycerin sublingual tablets need to be dissolved in the oral cavity before they can be absorbed, which makes the drug stay in the oral cavity for a short time and is easily removed by saliva, and affects the patient's compliance due to taste
Sprays and chewing gums have a short action time, and it is difficult for peptide and protein drugs to exert their curative effect without adding an ideal penetration-enhancing agent
Traditional tablets are prepared by tableting method, with a dense structure, which is not conducive to the release of drugs and limits the absorption of drugs
Patch drug loading is limited, not widely used

Method used

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  • Formula of oral mucosa absorbing dosage form of medicines of polypeptides and proteins, and preparation method and application thereof
  • Formula of oral mucosa absorbing dosage form of medicines of polypeptides and proteins, and preparation method and application thereof
  • Formula of oral mucosa absorbing dosage form of medicines of polypeptides and proteins, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Embodiment 1 screens penetration-enhancing absorbent

[0067] The TR146 oral mucosal epithelial cell osmotic transport model was used to study the absorption promotion. Aspirate the DMEM culture solution in the upper and lower chambers of the insert culture dish, and wash the TR146 cells with HBSS buffer. Then add HBSS solution into the upper and lower chambers respectively, after equilibrating for 1 hour, suck out the HBSS solution from the upper chamber, and add 2mL of the test solution (containing different concentrations of osmosis-absorbing agents). Take a sample of 100 μL from the lower chamber at the set time, and immediately add an equal amount of HBSS solution. Using chromatographic method, sample injection analysis, record the obtained peak area (A), and calculate the cumulative penetration of insulin at each time point. Calculate the following indicators according to the obtained data: ①Insulin apparent permeability coefficient: P app =dQ / dt×1 / (A×C 0 ); ②...

Embodiment 2

[0075] The cytotoxic effect of embodiment 2 permeation-enhancing absorption agent

[0076] Using TR146 cells in the exponential growth phase, prepare 2×10 4 cells / mL single-cell suspension, 100 μL per well was inoculated in a 96-well plate. After 48 hours, 80 μL of culture medium was supplemented, and then 20 μL of insulin-free test solution was administered. The preparation method of the test solution was the same as that in 2.2. After incubation for 48 hours, MTT detection was carried out at a detection wavelength of 490 nm. Taking the enzyme activity of untreated cells as 100%, calculate the enzyme activity of the cells treated with the test solution. Calculation formula: relative enzyme activity (%)=(OD 1 -OD 2 ) / (OD 3 -OD 4 ), OD 1 Refers to the OD value of the cells treated with the test solution, OD 2 Refers to the OD value of the test solution without cells, OD 3 Refers to the OD value of untreated cells, OD 4 Refers to the OD value of the blank well when the...

Embodiment 3

[0078] Preparation of Example 3 Insulin Oral Adhesive Tablet

[0079] Prescription Composition of Insulin Oral Adhesive Tablets (mg / tablet)

[0080]

[0081] According to the prescription design in the table, mix the solutions of various auxiliary materials evenly and pour them into the mold. The mold was pre-frozen in a -20°C refrigerator for 24 hours, and then freeze-dried for 24 hours with a freeze dryer to remove the solvent component in the solution, and the adhesive layer of the insulin oral adhesive sheet was obtained. Then, smear a waterproof layer on it, the waterproof layer is 10% ethyl cellulose solution (prepared with dehydrated alcohol), placed at room temperature until dehydrated alcohol evaporates completely, promptly obtains the insulin oral cavity adhesive double-layer tablet, puts in dry Store in a refrigerator at 4°C. See the preparation process Figure 7 .

[0082] Figure 7 It is a schematic diagram of the preparation method of insulin oral adhesiv...

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Abstract

The invention relates to a medicament formula of macromolecular medicines of polypeptides and proteins and the like delivered by oral mucosa, and a preparation method and application thereof. The medicament comprises the following components: medicines of polypeptides and proteins, a penetration and absorbing enhancer, a bioadhesive agent, a protease inhibitor and an additive. The medicament is an oral adhesive two-layer piece with an adhesive layer and a waterproof layer, and the preparation technique is a freeze drying method. The medicament is suitable for various medicines of proteins and polypeptides. The invention aims at improving bioavailability of the medicines of polypeptides and proteins absorbed by the oral mucosa, enhancing the stability of medicine preparation of polypeptides and proteins and lays the foundation for developing a non-injection administration preparation of the medicines of polypeptides and proteins.

Description

technical field [0001] The invention relates to a pharmaceutical composition, preparation method and application of macromolecular medicines such as polypeptides and proteins delivered through oral mucosa. Background technique [0002] With the development of genetic engineering drug research, protein and peptide drugs, as a class of drugs with great potential, are playing an increasingly important role in clinical treatment. However, due to the hydrolysis of protein and peptide drugs by gastrointestinal proteases, these drugs are basically ineffective orally. Clinically, the most commonly used method of administration of protein and polypeptide drugs is injection. When protein and peptide drugs are used to treat chronic diseases, such as using insulin to treat diabetes, long-term injection is very inconvenient and brings great inconvenience and pain to patients. Therefore, the development of various non-injection dosage forms of protein and polypeptide drugs is a hot spot...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/20A61K38/02A61K47/00
CPCY02A50/30
Inventor 罗晓星薛小燕周颖侯征孟静茹陈瑛瑛
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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