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CN-122005506-A - Intestinal patch loaded with radix pseudostellariae cyclopeptide B and preparation method and application thereof

CN122005506ACN 122005506 ACN122005506 ACN 122005506ACN-122005506-A

Abstract

The invention discloses a intestinal adhesive patch loaded with radix pseudostellariae cyclic peptide B, a preparation method and application thereof, wherein the preparation method mainly utilizes glycosylation modified column [6] arene and radix pseudostellariae cyclic peptide B to form a host-guest inclusion compound through interaction self-assembly of host-guest, and the composite patch with intestinal targeting and long-acting adhesion functions is prepared by loading the composite patch into a mucous membrane adhesion polymer matrix and adopting a tape casting technology. The intestinal adhesive patch prepared by the invention can control the drug release under the pH environment of intestinal tracts, and prolong the residence time in the intestinal tracts by means of the mucous membrane adhesion property of the high polymer material, thereby promoting the drug absorption. The preparation has simple process and good repeatability, and has industrial amplifying potential. The 'host-guest inclusion-patch delivery' double-layer system constructed by the invention can effectively protect the stability of the pseudostellaria root cyclic peptide B in a complex gastrointestinal tract environment, improve the oral bioavailability of the pseudostellaria root cyclic peptide B and provide a novel effective strategy for oral delivery of polypeptide drugs.

Inventors

  • CHEN YI
  • TANG LEI
  • GONG ZIPENG
  • HUANG YUANXING
  • CHEN WENZHANG
  • PENG JIANQING
  • SUN RUNBIN
  • Huang Cheneryu

Assignees

  • 贵州医科大学

Dates

Publication Date
20260512
Application Date
20260206

Claims (10)

  1. 1. The preparation method of the intestinal adhesive patch loaded with the pseudostellaria root cyclic peptide B is characterized by comprising the following steps of: (1) Modifying column [6] arene by using polysaccharide to obtain glycosylated column [6] arene, mixing glycosylated column [6] arene and pseudostellaria root cyclic peptide B in a solution, performing ultrasonic self-assembly to obtain a host-guest complex solution HB ⊂ P6-GalNAc, and performing freeze-drying to obtain HB ⊂ P6-GalNAc freeze-dried powder; (2) Mixing carbomer CP and hydroxypropyl methylcellulose HPMC in a solution to prepare a high molecular hydrogen bond compound IPC solution; (3) Mixing the HB ⊂ P6-GalNAc freeze-dried powder, the IPC solution and the additive to obtain a slow release layer solution; (4) And (3) preparing a backing layer, spreading the slow-release layer solution on the backing layer, drying and cutting to obtain the HB ⊂ P6-GalNAc/IPC intestinal adhesive patch, namely the intestinal adhesive patch loaded with the pseudostellaria root cyclic peptide B.
  2. 2. The method for preparing a pseudostellaria root cyclic peptide B-loaded intestinal adhesive sheet according to claim 1, wherein in the step (1), the polysaccharide is one or more selected from galactose, mannose and N-acetylgalactosamine.
  3. 3. The method for preparing the intestinal adhesive patch carrying the pseudostellaria root cyclic peptide B as claimed in claim 1, wherein in the step (1), the molar ratio of the glycosylation column [6] arene to the pseudostellaria root cyclic peptide B is (0.5-5): 1.
  4. 4. The preparation method of the intestinal adhesive patch loaded with the pseudostellaria root cyclic peptide B as claimed in claim 1, wherein in the step (1), the self-assembly condition is that the solution is stirred at a stirring speed of 300-1000 rpm, a temperature of 25-37 ℃ and a time of 2-12 h.
  5. 5. The preparation method of the intestinal adhesive patch loaded with pseudostellaria root cyclic peptide B according to claim 1, wherein in the step (2), the carbomer is selected from one or more of CPs 934 、CP 940 、CP 941 、CP 980 、CP 1340 、CP 2020 , preferably CP 940 , and the mass ratio of CP 940 to HPMC is 9:1-1:9 (w/w), preferably 3:1 (w/w).
  6. 6. The preparation method of the intestinal adhesive patch carrying the pseudostellaria root cyclic peptide B as claimed in claim 1, wherein in the step (2), the method of mixing in the solution is that a 50-70% ethanol solution is used as a dispersion medium to prepare a CP solution and an HPMC solution respectively, the HPMC solution is slowly added into the CP solution, the pH is regulated to 3-9, the mixture is stirred for 3-5h at the temperature of 25-35 ℃ to obtain the IPC solution, the concentration of the CP solution is 1-5% (w/v), and the concentration of the HPMC solution is 1-5% (w/v).
  7. 7. The preparation method of the intestinal adhesive patch carrying the pseudostellaria root cyclic peptide B as claimed in claim 1, wherein in the step (3), the mass ratio of HB ⊂ P6-GalNAc freeze-dried powder, IPC solution and additive is 2 (5-7): 0.1-1.5.
  8. 8. The preparation method of the intestinal adhesive patch carrying the pseudostellaria root cyclic peptide B as claimed in claim 1, wherein in the step (5), the preparation method of the backing layer comprises the steps of dissolving a film forming material in an organic solvent, adding an additive, uniformly stirring, forming a film, and preparing a waterproof backing layer; Preferably, the preparation method further comprises preparing a pigment layer solution using pigment and additives, spreading the pigment layer solution on a waterproof backing layer, and then spreading a slow release layer solution on the backing layer.
  9. 9. An intestinal adhesive patch loaded with pseudostellaria root cyclic peptide B, wherein the intestinal adhesive patch loaded with pseudostellaria root cyclic peptide B is prepared by the preparation method of any one of claims 1 to 8.
  10. 10. Use of the intestinal patch loaded with pseudostellaria root cyclic peptide B as claimed in claim 9 in the preparation of a hypoglycemic medicament.

Description

Intestinal patch loaded with radix pseudostellariae cyclopeptide B and preparation method and application thereof Technical Field The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an intestinal patch loaded with pseudostellaria root cyclic peptide B, and a preparation method and application thereof. Background Type 2 diabetes mellitus (T2 DM) is a complex metabolic disease whose central pathological features are progressive insulin resistance and islet beta cell failure, leading to a persistent hyperglycemic state. The disease becomes one of global great public health problems, is often accompanied by microvascular and macrovascular complications such as heart and kidney function injury, neuropathy and the like, seriously damages the life quality of patients and increases the medical burden. In the theory of traditional Chinese medicine, T2DM belongs to the category of diabetes, and pathogenesis is related to deficiency of both qi and yin and spleen dysfunction in transportation, which has been discussed in Su Wen-Qi disease theory. Radix Pseudostellariae (Pseudostellariae Radix) is used as a traditional medicinal material for supplementing qi and promoting the production of body fluid, and is commonly used for treating diabetes. Modern researches show that radix pseudostellariae contains various active ingredients such as cyclic peptide, polysaccharide, saponin and the like, wherein the radix pseudostellariae cyclic peptide B (Heterophyllin B, HB) is taken as a cyclic octapeptide compound, and has high affinity to dipeptidyl peptidase-4 (DPP-4) and glucagon-like peptide-1 receptor (GLP-1R) in molecular docking researches, which indicates that the radix pseudostellariae cyclic peptide B possibly participates in blood glucose regulation through inhibiting double mechanisms of DPP-4 enzyme activity and activating GLP-1R signals, and has good hypoglycemic potential. However, HB has the problems of poor water solubility, low membrane permeability, susceptibility to enzymolysis and degradation, and the like, so that the HB has low oral bioavailability and rapid in-vivo elimination, and severely limits the clinical application of the HB. Therefore, development of a delivery system capable of effectively improving the solubility, stability and oral absorption efficiency of HB has become an important topic for promoting the conversion of the active ingredient to clinic. In terms of the preparation form, an oral film (also called an oral patch) is a film-shaped preparation which has a specific shape and can realize local or systemic administration through mucoadhesive, and the definition of the film-shaped preparation is recorded in pharmacopoeia of the people's republic of China. The oral film is generally composed of film forming materials, plasticizers, medicines and functional auxiliary materials, and is prepared by casting, coating and other processes, and has the advantages of convenient carrying, simple administration, capability of avoiding first pass effect and the like. The two types of quick dissolving film and slow controlled releasing film are classified according to different releasing actions, the former is suitable for medicine needing quick acting, and the latter can realize continuous or controlled releasing at specific position through material and structure design. However, when the conventional oral film is used for polypeptide medicines such as HB, the problems of low drug loading, short gastrointestinal residence time, insufficient enzyme barrier capability and the like still exist, and high-efficiency delivery is difficult to realize. In order to prolong the acting time of HB in intestinal tract and improve the oral bioavailability, it is necessary to develop an oral film with the functions of mucosa adhesion, enzyme barrier protection and controllable release. Disclosure of Invention Aiming at the problems of poor stability, low absorption efficiency, insufficient targeting and the like in the oral delivery of polypeptides in the prior art, the invention provides an intestinal patch loaded with pseudostellaria root cyclic peptide B, and a preparation method and application thereof. The patch has the functions of intestinal targeting, enzyme protection and long-acting adhesion, and can remarkably improve the oral bioavailability of HB. The technical scheme is that in order to solve the technical problems, the invention adopts the following technical scheme: In a first aspect, the invention provides a preparation method of an intestinal adhesive patch loaded with pseudostellaria root cyclic peptide B, the method mainly utilizes glycosylation modified column [6] arene and HB to form a host-guest inclusion compound through interaction self-assembly of a host-guest body, the host-guest inclusion compound is loaded in a mucous membrane-adhesive polymer matrix, and a composite patch with intestinal targeting and long-acting adhesion functions i