CN106109400A - A kind of oral drugs hydrogel slow-released carrier and preparation method and applications - Google Patents

Abstract

The invention discloses a hydrogel slow-release carrier for oral medicine, a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. Using chitosan, dialdehyde starch, gelatin, and polyvinyl alcohol as raw materials, mix them in proportion to form a homogeneous solution, and take it orally into the stomach to quickly form a gel, which can wrap and release the drug contained in it, and reduce the high drug concentration. damage to receptors. The drug can be released slowly in the stomach, and is especially suitable for treating stomach diseases.

Description

Hydrogel slow-release carrier for oral medicine, preparation method and application thereof

technical field

The invention belongs to the technical field of pharmaceutical preparations, and relates to a hydrogel slow-release carrier for oral medicine, a preparation method and application thereof.

Background technique

Ordinary administration methods, the drug is continuously released in high concentration in the body, the maintenance time is short, and the fluctuation is large, which may easily cause the receptor sensitivity to decrease, not only fail to achieve the desired curative effect, but may also produce drug resistance and even side effects . The drug controlled release system uses certain materials as the carrier to make the drug into a certain dosage form. The drug sustained release carrier can control the release of the drug in the body, so that the drug can be slowly released in the body at a certain speed within an appropriate time according to the set dose. Release, prolong drug action time, reduce drug degradation and loss, reduce drug side effects, improve drug utilization, produce stable blood drug concentration, reduce the number of administrations, and thus treat a certain disease more effectively. Therefore, it is very important to prepare a drug carrier that can release the loaded drug slowly.

A hydrogel with a three-dimensional cross-linked network does not dissolve in an aqueous solution, can maintain a certain shape, but can swell and absorb water, has a unique temperature and pH response behavior, and the aqueous environment of the hydrogel is suitable for polar drug molecules. Diffusion, so it can be used as a drug controlled release system. CN103467755A discloses "a drug slow-release hydrogel and its preparation method and application". The high-voltage electrostatic droplet method is used to prepare monodisperse drug-containing calcium alginate microspheres, and then the drug-loaded calcium alginate microspheres are placed in the In the hydrogel network structure, so as to realize the sustained release of drugs, it has good elasticity, water absorption and water retention, breathable and water permeable properties; but calcium alginate is not easily soluble in water, and its preparation process is cumbersome. CN101214217A discloses "hydrogel-hydrogel composite material and its preparation method and drug slow-release matrix application", although it is convenient to carry and use, and has a long storage time, its application range is small, and it is only suitable for slow-release of corneal contact lenses Eye drops; and initiators and cross-linking agents are likely to remain in the carrier, and the biocompatibility is poor. Injectable sodium alginate/sulfurized fructose-chitosan composite hydrogel prepared as an oral carrier of protein drugs by Zhang Yinye et al. Gel, when the pH value is 6.8 and 7.4, the release rate of bovine serum albumin (BSA) increases, and can be used as a kind of oral protein drug carrier, but the process that chitosan is converted into sulfurated fructose-chitosan is relatively difficult. complex. According to the review, although hydrogel can be used as a good drug carrier, the hydrogel drug carrier needs to be further improved, and a more suitable drug carrier needs to be invented.

Contents of the invention

In order to solve the above technical problems, the purpose of the invention is to provide an oral drug hydrogel sustained-release carrier, a preparation method and its application to address the shortcomings of the existing hydrogel drug sustained-release carrier.

In order to solve one of the above-mentioned technical problems, the technical solution proposed is: a hydrogel sustained-release carrier for oral medicine, which is characterized in that: it is prepared from chitosan, dialdehyde starch, gelatin, and polyvinyl alcohol as raw materials. The volume ratio is 30%-50% of chitosan, 5%-20% of dialdehyde starch, 10%-40% of gelatin and 5%-15% of polyvinyl alcohol.

Preferably, the deacetylation degree of the chitosan is greater than 85%.

Preferably, the purity of the dialdehyde starch, gelatin and polyvinyl alcohol all reach the pharmaceutical standard.

The technical scheme proposed in order to solve one of the above-mentioned technical problems is: a preparation method of a hydrogel slow-release carrier for oral medicine, comprising the following steps:

(1) Prepare solution: prepare the aqueous solutions of chitosan, dialdehyde starch, gelatin and polyvinyl alcohol with a mass fraction of 2.0 to 8.0% respectively;

(2) mixed solution: chitosan solution is mixed with dialdehyde starch solution to form chitosan/dialdehyde starch mixed solution, then add gelatin solution, and finally add polyvinyl alcohol solution;

(3) Cross-linking: Mix the mixed solution composed of chitosan, dialdehyde starch, gelatin and polyvinyl alcohol evenly, place it in an acidic solution, cross-linking will occur rapidly, and take out after forming a stable and uniform hydrogel;

(4) Washing: Wash the hydrogel with ultrapure water until it becomes neutral to obtain the finished hydrogel.

Preferably, the pH of the acidic solution is not higher than 4.

The technical solution proposed in order to solve one of the above technical problems is: the application of a hydrogel sustained-release carrier for oral medicine, and the application of the hydrogel sustained-release carrier for oral medicine in oral drug carrier drugs.

Preferably, the application of the hydrogel slow-release carrier for oral medicine in the preparation of medicine for treating stomach diseases.

Beneficial effect:

1. The hydrogel of the present invention takes chitosan and dialdehyde starch as main raw materials, wherein chitosan is a derivative of chitin, and the natural yield of chitosan is high, non-toxic, non-irritating, non-immunogen, and non-pyrogenic Reactive, non-hemolytic, non-mutagenic, and naturally degradable, with excellent tissue compatibility; dialdehyde starch is modified by starch, which is a renewable and degradable material with certain viscosity , film-forming, gelling and adhesive properties. In addition, using water as a solvent, chitosan and dialdehyde starch will cross-link under the catalysis of acidic conditions to form a gel, that is, chitosan and dialdehyde starch can form a gel in the gastric juice environment, and the formation process is harmless. It has typical pH value response characteristics, and the whole preparation process is simple. Therefore, the acidic gastric juice environment is the natural catalytic environment for the cross-linking of chitosan and dialdehyde starch to form a gel, which is suitable for oral drug carriers. Gelatin and polyvinyl alcohol can further optimize the performance of the hydrogel. The drug is wrapped in the hydrogel network so that water cannot quickly enter the interior to dissolve the drug. The drug is released with the slow degradation of the hydrogel. Hydrogel drug carrier.

2. Raw materials are easy to obtain: the chitosan used is a derivative of chitin, which is rich in resources; dialdehyde starch and gelatin are natural polymer materials, which are easy to obtain widely. The raw materials are non-toxic, non-irritating, non-immunogenic, and have excellent biocompatibility and degradation performance.

3. Using water as a solvent, mix the raw materials in proportion, and catalyze cross-linking into a gel in an acidic environment. The whole preparation process is simple.

4. The acidic environment is the catalyst environment for the formation of hydrogel, and the hydrogel is suitable for the carrier of oral medicine, especially for the treatment of stomach diseases.

5. If the degree of deacetylation of chitosan is greater than 85%, the solubility of chitosan is high, which is beneficial to the subsequent crosslinking. The purity of the dialdehyde starch, gelatin and polyvinyl alcohol all reach the pharmaceutical standard, ensuring high purity.

Description of drawings

Fig. 1 is the infrared spectrogram of embodiment 1 chitosan, dialdehyde starch, composite hydrogel.

Fig. 2 is the scanning electron micrograph of the cross-section of the hydrogel after freeze-drying in Example 2.

Fig. 3 is a scanning electron micrograph of the surface of the hydrogel after freeze-drying in Example 3.

detailed description

Below in conjunction with the examples, the present invention will be further described in detail, but the implementation is not limited thereto, and all technologies and prepared materials based on the above contents of the present invention all belong to the protection scope of the present invention.

Example 1

The degree of deacetylation of the chitosan is greater than 85%, and the purity of the dialdehyde starch, gelatin and polyvinyl alcohol all reach the pharmaceutical standard. 2g chitosan, 2g dialdehyde starch, 2g gelatin, and 2g polyvinyl alcohol were dissolved in 50g deionized water respectively, and the prepared chitosan solution, dialdehyde starch solution, gelatin solution, and polyvinyl alcohol solution were mixed in 5: The volume ratio of 0.8:3:0.5 is mixed evenly. Put the prepared solution into an acidic aqueous solution with a pH of 3.0 to catalyze cross-linking, leave it for 5 minutes to obtain a hydrogel, soak it in deionized water several times to neutrality, and obtain a finished hydrogel, freeze-dry it, and The dried hydrogel was subjected to infrared spectrum analysis (results are shown in accompanying drawing 1). It can be seen from the figure that the vibration peak at 1450-1670 cm ^-1 confirms the existence of Schiff base (ie, imine bond), which proves that a stable imine bond is formed in the hydrogel.

Example 2

2g chitosan, 2g dialdehyde starch, 2g gelatin, and 2g polyvinyl alcohol were dissolved in 50g deionized water respectively, and the prepared chitosan solution, dialdehyde starch solution, gelatin solution, and polyvinyl alcohol solution were mixed in 5: The volume ratio of 1.2:3.5:0.6 is mixed evenly. Add the prepared solution to an acidic solution with a pH of 4.0 to catalyze it. After standing for 5 minutes, a hydrogel is obtained. Soak it in deionized water until neutral to obtain a finished hydrogel. After freeze-drying, it will be brittle after cooling with liquid nitrogen. , to expose the fracture surface, and carry out scanning electron microscope analysis on the hydrogel fracture surface (results are shown in Figure 2). It can be seen from the figure that the cross-section of the hydrogel is a multilayer structure with a large number of cavities, which proves that the hydrogel has excellent water absorption and swelling properties.

Example 3

2g chitosan, 2g dialdehyde starch, 2g gelatin, and 2g polyvinyl alcohol were dissolved in 50g deionized water respectively, and the prepared chitosan solution, dialdehyde starch solution, gelatin solution, and polyvinyl alcohol solution were mixed in 5: The volume ratio of 1.6:4:0.7 is evenly mixed. The prepared solution is added to an acidic solution with a pH of 3 for catalysis, and the hydrogel is obtained after standing for 5 minutes, soaked in deionized water until neutral, and the finished hydrogel is obtained. After lyophilization, the surface of the hydrogel was scanned by an electron microscope (results are shown in Figure 3). It can be seen from the figure that the microscopic surface of the hydrogel surface is smooth, and the fractures are relatively regular.

According to the above content, on the premise of not departing from the above-mentioned basic technical idea of the present invention, according to the general knowledge and technical means in this field, adding other biocompatible and therapeutic drug components to the hydrogel belongs to the content of the present invention Various modifications, substitutions and changes all belong to the scope of the present invention.

Claims (7)

1. an oral drugs hydrogel slow-released carrier, it is characterised in that: by chitosan, dialdehyde starch, gelatin, polyvinyl alcohol Be prepared from for raw material, the volume proportion of raw material be chitosan 30%～50%, dialdehyde starch 5%～20%, gelatin 10%～ 40%, polyvinyl alcohol 5%～15%.

Oral drugs hydrogel slow-released carrier the most according to claim 1, it is characterised in that: the de-second of described chitosan Acyl degree is more than 85%.

Oral drugs hydrogel slow-released carrier the most according to claim 1, it is characterised in that: described dialdehyde starch, bright Glue, the purity of polyvinyl alcohol all reach medicinal standard.

4. according to a preparation method for the arbitrary described oral drugs hydrogel slow-released carrier of claims 1 to 3, its feature It is to comprise the steps:

(1) preparation solution: preparation mass fraction is 2.0～the chitosan of 8.0%, dialdehyde starch, gelatin, polyvinyl alcohol respectively Aqueous solution；

(2) mixed solution: mixed with dialdehyde starch solution by chitosan solution, forms chitosan/dialdehyde starch mixed solution, then Add gelatin solution body, be eventually adding poly-vinyl alcohol solution；

(3) crosslinking: the mixed solution mix homogeneously being made up of chitosan, dialdehyde starch, gelatin and polyvinyl alcohol, is placed in acidity In solution, will crosslink rapidly, take out after forming the hydrogel of stable and uniform；

(4) washing: with milli-Q water hydrogel to neutral, i.e. obtain hydrogel finished product.

The preparation method of oral drugs hydrogel slow-released carrier the most according to claim 4, it is characterised in that: acid molten Liquid pH is not higher than 4.

6. according to the application of hydrogel slow-released carrier of the oral drugs described in claim 1-3, it is characterised in that: described oral Medicine hydrogel slow-released carrier application in oral drugs carrier medicament.

7. according to the application of hydrogel slow-released carrier of the oral drugs described in claim 1-3, it is characterised in that: described oral Medicine hydrogel slow-released carrier is preparing the application treated in disease of stomach medicine.