Medicine for preventing stenosis after endoscopic submucosal dissection of early esophageal cancer and preparation method thereof

Abstract

The invention relates to the technical field of biomedicine, in particular to a medicine for preventing stenosis after endoscopic submucosal dissection of early esophageal cancer and a preparation method of the medicine, and provides a compound medicine based on a multi-target synergistic mechanism, and the occurrence rate of stenosis after ESD (Electro-Static Discharge) is remarkably reduced through anti-fibrosis, anti-inflammatory and tissue repair triple pathways. A unique nano coating technology realizes slow release and controlled release, the drug effect lasts for 72 hours or more, and systemic side effects are avoided. Animal experiments show that the composition has a better comprehensive curative effect than the existing therapy, and has a good clinical transformation prospect.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to a drug for preventing stenosis after endoscopic submucosal dissection of early esophageal cancer and a preparation method thereof. Background Art

[0002] Esophageal cancer is one of the most common malignant tumors in the world. Its early detection and treatment are crucial to prognosis. Endoscopic submucosal dissection (ESD) is the preferred treatment for early esophageal cancer. It uses endoscopic minimally invasive technology to completely remove lesions confined to the mucosal layer or submucosal layer to achieve radical treatment. ESD has the advantages of less trauma, faster recovery, and preservation of esophageal function. The postoperative recovery rate can reach more than 90%, and it can provide accurate pathological evaluation to guide subsequent treatment.

[0003] Indications for ESD include: tumor diameter ≤ 3 cm, invasion depth ≤ submucosal layer (SM1), no risk of lymph node metastasis, and lesion range suitable for endoscopic operation. The surgical process covers preoperative evaluation, submucosal injection dissection, wound treatment and postoperative follow-up, and the resection range must be strictly controlled to avoid complications such as stenosis. Studies have shown that the risk of metachronous multiple primary cancers after ESD is related to the length of the lesion, the spotty iodine-unstained area, and inflammatory indicators, and needs to be monitored through regular endoscopic review.

[0004] Although ESD technology has significantly improved the cure rate of early esophageal cancer, it still needs to be combined with lifestyle intervention (such as quitting smoking and limiting alcohol) to reduce the risk of recurrence, and develop individualized comprehensive treatment plans for high-risk patients.

[0005] Existing methods for preventing stenosis after ESD surgery have significant defects:

[0006] 1. Limitations of single-target therapy: Traditional hormonal anti-inflammatory drugs (such as glucocorticoids) can only control inflammatory responses in the short term and cannot inhibit fibrosis caused by scar formation;

[0007] 2. Physical therapy has serious side effects: dilatation and stent placement are prone to cause secondary injury and infection risks;

[0008] 3. High cost of biological agents: Growth factor repair agents are expensive and have poor stability.

[0009] The present invention innovatively combines anti-fibrosis, plant-derived anti-inflammatory and tissue repair components to construct a multi-pathway synergistic system, thereby fundamentally blocking the pathological process of stenosis formation. Summary of the invention

[0010] In order to solve the above problems, the present invention first provides a drug for preventing stenosis after endoscopic submucosal dissection of early esophageal cancer, comprising an anti-fibrosis component, a plant anti-inflammatory component and a tissue repair component of a biological extract.

[0011] In certain embodiments, the anti-fibrotic component is selected from colchicine or becipiril.

[0012] In certain embodiments, the botanical anti-inflammatory ingredient is selected from tanshinone ⅡA or curcumin.

[0013] In certain embodiments, the tissue repair component is selected from collagen peptides or umbilical cord mesenchymal stem cell extracts.

[0014] In certain embodiments, the mass ratio of the anti-fibrosis component, the plant anti-inflammatory component and the tissue repair component of the biological extract is (5-30):(10-40):(20-40).

[0015] In certain embodiments, the drug further comprises xanthan gum and hypromellose as sustained-release carriers.

[0016] The present invention also provides a method for preparing the above-mentioned medicine, which comprises a two-step process of nanoemulsification and pH-responsive coating.

[0017] Compared with the prior art, the present invention has at least the following beneficial effects:

[0018] The present invention innovatively combines anti-fibrosis, plant-derived anti-inflammatory and tissue repair components to construct a multi-pathway synergistic system, thereby fundamentally blocking the pathological process of stenosis formation. DETAILED DESCRIPTION

[0019] In order to make the technical problems to be solved, technical solutions and advantages of the present invention more clear, they are described in detail below in conjunction with specific embodiments.

[0020] Example 1 Pharmaceutical Composition

[0021] This medicine contains the following active ingredients in the following percentages by mass:

[0022]

[0023]

[0024] Among them, the anti-fibrosis group inhibited excessive collagen deposition; the plant anti-inflammatory group reduced the release of inflammatory factors (TNF-α, IL-6); and the collagen peptide / umbilical cord mesenchymal stem cell extract in the tissue repair group promoted epithelial cell regeneration.

[0025] (II) Preparation method

[0026] Step 1: Active ingredient pretreatment

[0027] Dissolve colchicine in DMSO to form a homogeneous solution;

[0028] Ultrasonic-assisted extraction was used to purify tanshinone ⅡA from salvia miltiorrhiza (power 30kHz, time 20min);

[0029] Through supercritical CO 2 Curcumin was obtained by extraction method (pressure 30 MPa, temperature 45°C).

[0030] Step 2: Nanoemulsion preparation

[0031] The above ingredients are emulsified with a biocompatible substrate (such as PLGA) using a high-pressure homogenizer (8000 psi) to form drug-loaded microspheres with a particle size of 100-200 nm and an encapsulation rate of ≥85%.

[0032] Step 3: Sustained release layer coating

[0033] Electrospinning technology was used to wrap the outer layer with a pH-responsive chitosan film (the dissolution rate increased by 30% at pH 5.5).

[0034] Step 4: Formulation

[0035] The nano-microspheres are mixed with excipients and compressed into tablets or made into oral liquid preparations.

[0036] (III) Pharmacodynamic Verification

[0037] Animal experiments show that:

[0038] The incidence of stenosis in the treatment group was 62% lower than that in the control group 4 weeks after surgery (P<0.01);

[0039] HE staining showed that the thickness of the new mucosa increased by 1.8 times;

[0040] ELISA test showed that IL-1β level decreased by 58%.

[0041] Example 2 Pharmaceutical Composition

[0042] This medicine contains the following active ingredients in the following percentages by mass:

[0043]

[0044]

[0045] Among them, the anti-fibrosis group inhibited excessive collagen deposition; the plant anti-inflammatory group reduced the release of inflammatory factors (TNF-α, IL-6); and the collagen peptide / umbilical cord mesenchymal stem cell extract in the tissue repair group promoted epithelial cell regeneration.

[0046] (II) Preparation method

[0047] Step 1: Active ingredient pretreatment

[0048] Dissolve colchicine in DMSO to form a homogeneous solution;

[0049] Ultrasonic-assisted extraction was used to purify tanshinone ⅡA from salvia miltiorrhiza (power 30kHz, time 20min);

[0050] Through supercritical CO 2 Curcumin was obtained by extraction method (pressure 30 MPa, temperature 45°C).

[0051] Step 2: Nanoemulsion preparation

[0052] The above ingredients are emulsified with a biocompatible substrate (such as PLGA) using a high-pressure homogenizer (8000 psi) to form drug-loaded microspheres with a particle size of 100-200 nm and an encapsulation rate of ≥85%.

[0053] Step 3: Sustained release layer coating

[0054] Electrospinning technology was used to wrap the outer layer with a pH-responsive chitosan film (the dissolution rate increased by 30% at pH 5.5).

[0055] Step 4: Formulation

[0056] The nano-microspheres are mixed with excipients and compressed into tablets or made into oral liquid preparations.

[0057] (III) Pharmacodynamic Verification

[0058] Animal experiments show that:

[0059] The incidence of stenosis in the treatment group was 56% lower than that in the control group 4 weeks after surgery (P<0.01);

[0060] HE staining showed that the thickness of the new mucosa increased by 1.5 times;

[0061] ELISA test showed that IL-1β level decreased by 55%.

[0062] Example 3 Pharmaceutical Composition

[0063] This medicine contains the following active ingredients in the following percentages by mass:

[0064]

[0065] Among them, the anti-fibrosis group inhibited excessive collagen deposition; the plant anti-inflammatory group reduced the release of inflammatory factors (TNF-α, IL-6); and the collagen peptide / umbilical cord mesenchymal stem cell extract in the tissue repair group promoted epithelial cell regeneration.

[0066] (II) Preparation method

[0067] Step 1: Active ingredient pretreatment

[0068] Dissolve colchicine in DMSO to form a homogeneous solution;

[0069] Ultrasonic-assisted extraction was used to purify tanshinone ⅡA from salvia miltiorrhiza (power 30kHz, time 20min);

[0070] Through supercritical CO 2 Curcumin was obtained by extraction method (pressure 30 MPa, temperature 45°C).

[0071] Step 2: Nanoemulsion preparation

[0072] The above ingredients are emulsified with a biocompatible substrate (such as PLGA) using a high-pressure homogenizer (8000 psi) to form drug-loaded microspheres with a particle size of 100-200 nm and an encapsulation rate of ≥85%.

[0073] Step 3: Sustained release layer coating

[0074] Electrospinning technology was used to wrap the outer layer with a pH-responsive chitosan film (the dissolution rate increased by 30% at pH 5.5).

[0075] Step 4: Formulation

[0076] The nano-microspheres are mixed with excipients and compressed into tablets or made into oral liquid preparations.

[0077] (III) Pharmacodynamic Verification

[0078] Animal experiments show that:

[0079] The incidence of stenosis in the treatment group was 52% lower than that in the control group 4 weeks after surgery (P<0.01);

[0080] HE staining showed that the thickness of the new mucosa increased by 1.6 times;

[0081] ELISA test showed that IL-1β level decreased by 52%.

[0082] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A drug for preventing stenosis after endoscopic submucosal dissection of early esophageal cancer, characterized in that: Contains anti-fibrotic ingredients, plant anti-inflammatory ingredients and tissue repair ingredients from biological extracts.

2. The drug according to claim 1, characterized in that The anti-fibrotic component is selected from colchicine or becipiril.

3. The drug according to claim 1, characterized in that The plant anti-inflammatory component is selected from tanshinone ⅡA or curcumin.

4. The drug according to claim 1, characterized in that The tissue repair component is selected from collagen peptides or umbilical cord mesenchymal stem cell extracts.

5. The drug according to claim 1, characterized in that The mass ratio of the anti-fibrosis component, the plant anti-inflammatory component and the tissue repair component of the biological extract is (5-30):(10-40):(20-40).

6. The drug according to claim 1, characterized in that The drug also contains xanthan gum and hypromellose as sustained-release carriers.

7. A method for preparing the drug according to any one of claims 1 to 6, characterized in that: It includes two-step processes: nanoemulsification and pH-responsive coating.

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