A moisture environment stable adhesive medical gel and a preparation method thereof

Abstract

The present application relates to the field of medical adhesive, especially to a moisture environment stable adhesive medical gel and its preparation method. The moisture environment stable adhesive medical gel is a cyanoacrylate-based gel including at least 18-24 wt% of a composite thickening composition. The medical gel provided in the present application has suitable viscosity and good human body affinity, and the underwater viscosity and adhesion reach excellent clinical use standards, and the phenomenon of poor viscosity during use cannot be used, and it helps to reduce the discomfort of the human body.

Description

Technical Field

[0001] This invention relates to the field of medical adhesives, and more particularly to a medical gel that is stable in a moisture environment and its preparation method. Background Technology

[0002] The advent of medical adhesives revolutionized surgical procedures, moving from sutures to direct bonding. Among these, medical adhesives based on cyanoacrylates, in particular, have gained widespread application due to their excellent non-toxicity, antibacterial properties, and rapid bonding at room temperature. However, with the development of clinical medicine and the increasing number of application scenarios, the weaknesses of cyanoacrylate-based medical gels / adhesives have gradually become apparent.

[0003] In the prior art, Chinese patent CN112354001B provides a cyanoacrylate-based medical adhesive, which uses stabilizer-loaded porous polylactic acid microspheres and cyanoacrylate to prepare a medical adhesive with stabilizer slow release and avoidance of adverse effects on the human body. However, the use of hydrophobic polylactic acid microspheres will significantly affect the adhesiveness, consistency and mechanical properties of the medical adhesive in an aqueous environment, resulting in varying degrees of decline in the above properties.

[0004] Therefore, in order to avoid the above problems, this application provides a medical matrix gel that can be stably bonded in a moisture environment and a method for preparing the same. Summary of the Invention

[0005] To address the aforementioned problems, the first aspect of this invention provides a medical gel that is stable in a moisture environment and is a cyanoacrylate-based gel comprising at least 18-24 wt% of a composite thickening composition.

[0006] As a preferred embodiment, the composite thickening composition is a combination thickener obtained by compounding at least three thickeners.

[0007] As a preferred embodiment, the combined thickener is a compound composition of at least three of the following: sodium polyacrylate, povidone, β-cyclodextrin, magnesium stearate, colloidal silica, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, hydroxypropyl cellulose, polycaprolactone, guar gum, gelatin, guar gum, carrageenan, gum arabic, tamarind gum, guar gum, dimethyl phthalate, triethyl phthalate, ethyl oleate, and triethyl citrate.

[0008] As a preferred embodiment, the combined thickener is a compound composition of povidone, ethyl oleate, and triethyl citrate.

[0009] As a preferred embodiment, the mass ratio of the polyvinyl ether, ethyl oleate, and triethyl citrate is 0.3–3:2–6:12–18.

[0010] As a preferred embodiment, the mass ratio of the polyvinyl ether, ethyl oleate and triethyl citrate is 0.8-1.5:3-4:13-16.

[0011] As a preferred embodiment, the mass ratio of the polyvinyl ether, ethyl oleate, and triethyl citrate is 1:3.5:14.

[0012] In this application, by using a thickening compound of povidone, ethyl oleate, and triethyl citrate as the preparation raw material, the adhesion and curing time of the medical gel in a moist environment can be effectively improved, while maintaining good mechanical properties. The applicant believes that when the mass ratio of povidone, ethyl oleate, and triethyl citrate is 1:3.5:14, the long-chain structure of povidone can preferentially integrate into triethyl citrate in the above compound, thus penetrating and distributing more deeply within the cyanoacrylate matrix. Furthermore, with the combined regulating effect of ethyl oleate and triethyl citrate on the cyanoacrylate matrix, the viscosity and adhesion of the system are enhanced while reducing its impact on the surface properties of the matrix. This also avoids excessive viscosity and bottom sedimentation caused by excessive molecular chain entanglement due to the addition of povidone.

[0013] As a preferred embodiment, the mass ratio of the composite thickening composition to the cyanoacrylate-based gel is 18–21:79–82.

[0014] As a preferred embodiment, the mass ratio of the composite thickening composition to the cyanoacrylate-based gel is 18.5:81.5.

[0015] As a preferred embodiment, the cyanoacrylate-based gel is a compound composition of any one of α-cyanoacrylate n-butyl ester, α-cyanoacrylate n-octyl ester, α-cyanoacrylate isooctyl ester, α-cyanoacrylate tert-butyl ester, and α-cyanoacrylate heptyl ester with their corresponding polymers.

[0016] As a preferred embodiment, the cyanoacrylate-based gel is a compound composition of n-butyl α-cyanoacrylate and poly(n-butyl α-cyanoacrylate).

[0017] As a preferred embodiment, the mass ratio of α-cyanoacrylate to poly(α-cyanoacrylate) is 15-18:64-66.

[0018] As a preferred embodiment, the mass ratio of α-cyanoacrylate to poly(α-cyanoacrylate) is 16:65.5.

[0019] As a preferred embodiment, the poly(α-cyanoacrylate) n-butyl ester is poly(α-cyanoacrylate) n-butyl ester polymerized by irradiation, and the irradiation dose of the irradiation polymerization is 10-12 kGy / h.

[0020] As a preferred embodiment, the irradiation dose for the irradiation polymerization of the poly(α-cyanoacrylate) n-butyl ester is 11 kGy / h.

[0021] The second aspect of the present invention provides a method for preparing the above-mentioned moisture-stable and adhesive medical gel, comprising the following steps: adding a composite thickening composition to a cyanoacrylate-based gel, mixing and stirring until completely dissolved, thereby obtaining the gel.

[0022] Beneficial effects:

[0023] 1. The medical gel provided in this invention has suitable viscosity and good human affinity. Its underwater viscosity and adhesion meet excellent clinical use standards. It will not cause the phenomenon of poor viscosity that makes it unusable during use, and it helps to reduce discomfort at the application site.

[0024] 2. The medical gel provided in this invention has a simple mixing and preparation method, and the product has moderate viscosity, good underwater adhesion, convenient operation, and relatively fast process. It can be easily scaled up for industrial production and has excellent market prospects.

[0025] 3. The medical gel provided in this invention can maintain excellent hemostatic performance and excellent curing film formation speed, quickly forming a hemostatic protective film with excellent mechanical strength, and is less likely to cause microcatheter blockage and ectopic embolism during use.

[0026] 4. The medical gel provided in this invention has excellent moisture environment performance, which can ensure that it still maintains excellent applicability in specific clinical use environments, thus expanding its application environment and field in the field of medical adhesives.

[0027] 5. The medical gel provided in this invention, by using a thickening compound of povidone, ethyl oleate and triethyl citrate as the preparation raw material, can effectively improve the adhesion and curing time of the medical gel in a moist environment. When the mass ratio of povidone, ethyl oleate and triethyl citrate is 1:3.5:14, the long chain structure of povidone can preferentially integrate into triethyl citrate in the above compound, thereby penetrating and distributing more deeply in the cyanoacrylate matrix. Furthermore, with the joint regulating effect of ethyl oleate and triethyl citrate on the cyanoacrylate matrix, the viscosity and adhesion of the system are enhanced while reducing its impact on the surface properties of the system matrix. Detailed Implementation

[0028] Example 1

[0029] Example 1 provides a medical gel that is stable in a moisture environment and has good adhesion. The raw materials, by weight, include: 18.5 parts of a composite thickening composition and 81.5 parts of cyanoacrylate-based gel.

[0030] The composite thickening composition is a compound of polyvinyl oleate, ethyl oleate and triethyl citrate, in a mass ratio of 1:3.5:14.

[0031] The cyanoacrylate-based gel is a compound composition of n-butyl α-cyanoacrylate and poly(n-butyl α-cyanoacrylate) in a mass ratio of 16:65.5.

[0032] The poly(α-cyanoacrylate) n-butyl ester is a poly(α-cyanoacrylate) n-butyl ester polymerized by irradiation, with an irradiation dose of 11 kGy / h.

[0033] In this embodiment, povidone was purchased from Ashland (China) Investment Co., Ltd. as the K29 product.

[0034] In this embodiment, α-cyanoacrylate n-butyl ester was purchased from Beijing Fuaile Company.

[0035] In this embodiment, the triethyl citrate was purchased from Shandong Kexing Chemical Co., Ltd. as a pharmaceutical excipient-grade triethyl citrate product.

[0036] The second aspect of this embodiment provides a method for preparing the above-mentioned moisture-stable and adhesive medical gel. The preparation steps are as follows: add the composite thickening composition to the cyanoacrylate-based gel, mix and stir until completely dissolved, and the gel is obtained.

[0037] Example 2

[0038] The specific implementation method of this embodiment is the same as that of embodiment 1, except that: in the raw material formula: the composite thickening composition is a compound composition of polyvinyl ketone, ethyl oleate and triethyl citrate, and the mass ratio of the three is 1.5:4:13.

[0039] Comparative Example 1

[0040] The specific implementation method of this comparative example is the same as that of Example 1, except that the composite thickening composition is a compound composition of polyvinyl ketone, ethyl oleate and triethyl citrate, with a mass ratio of 4.5:5:9.

[0041] Comparative Example 2

[0042] The specific implementation method of this comparative example is the same as that of Example 1, except that: in the raw material formula, the composite thickening composition is a compound composition of polyvinyl ketone, ethyl oleate and triethyl citrate, and the mass ratio of the three is 0.2:5.3:13.

[0043] Performance Evaluation

[0044] Wound closure strength: The wound closure strength of the medical gels prepared in the examples and comparative examples was tested according to the product requirements of "Medical Adhesive" YY / T 0729.1-2009. The medical gels were kept moist during the test according to the requirements. Ten samples were tested for each example and comparative example. The average value of the measured values ​​was recorded as an integer in Table 1.

[0045] Film-forming curing time: The film-forming curing time of the medical gels prepared in the examples and comparative examples was tested according to the product requirements of "Medical Adhesives" YY / T 0729.1-2009. Ten samples were tested for each example and comparative example, and the average value of the measured values ​​was recorded in Table 1.

[0046] Table 1

[0047] Example Wound closure strength (N) Film curing time (s) Example 1 37 2.3 Example 2 36 2.5 Comparative Example 1 24 4.5 Comparative Example 2 25 4.7

Claims

1. A medical gel that is stable in a moisture environment and adheres well, characterized in that: Medical gels are cyanoacrylate-based gels comprising at least 18-24 wt% of a composite thickening composition; The composite thickening composition is a compound composition of polyvinyl oleate, ethyl oleate and triethyl citrate; The mass ratio of polyvinyl oleate, ethyl oleate, and triethyl citrate is 0.8–1.5:3–4:13–16. The cyanoacrylate gel is a compound composition of n-butyl α-cyanoacrylate and poly(n-butyl α-cyanoacrylate); the mass ratio of n-butyl α-cyanoacrylate to poly(n-butyl α-cyanoacrylate) is 15-18:64-66.

2. The medical gel with stable adhesion in a moisture environment according to claim 1, characterized in that: The mass ratio of the composite thickening composition to the cyanoacrylate gel is 18–21:79–82.

3. A method for preparing a medical gel with stable adhesion in a moisture environment according to any one of claims 1 to 2, characterized in that: Preparation steps: Add the composite thickening composition to the cyanoacrylate-based gel, mix and stir until completely dissolved, and the product is obtained.