Application of colon-specific film coating premix in preparation of curcumin tablets

Abstract

The invention provides an application of a colon-specific film coating premix in preparation of curcumin tablets. The colon positioning type film coating premixing agent is prepared from the following components in parts by weight: 55 to 75 parts of a film forming material, 8 to 22 parts of a plasticizer, 5 to 15 parts of a coloring agent, 1 to 5 parts of a dispersing agent, 5 to 9 parts of an anti-sticking agent and 35 to 65 parts of a solvent, the film-forming material comprises polyacrylic resin II, polyacrylic resin III, methacrylic acid and methyl methacrylate (1: 1) copolymer type A and methacrylic acid and methyl methacrylate (1: 2) copolymer type B. When the provided colon-specific film coating premix is applied to curcumin tablets, the dissolution of curcumin in intestinal tracts can be improved, and the bioavailability of medicines can be improved.

Description

Technical Field

[0001] The invention relates to the field of pharmaceutical preparations, and in particular to application of a colon-localized film coating premix in the preparation of curcumin tablets. Background Art

[0002] Traditional oral or rectal administration not only has great toxic side effects, but also has problems such as poor specificity and difficulty in patient acceptance. Colon-targeted drug delivery directly delivers drugs to the affected area, which can improve drug efficacy or reduce dosage, while also reducing adverse reactions and making it easier for patients to use.

[0003] Colon targeted drug delivery is to use a drug delivery system to deliver the drug to the ileocecal region of the human body, where it will disintegrate and release after oral administration, and then exert local or systemic therapeutic effects in the large intestine. Since the 1990s, colon targeted drug delivery systems have received increasing attention, forming a variety of drug delivery types and developing a variety of targeted materials.

[0004] Curcumin is a polyphenol compound extracted from the rhizome of turmeric (Curcuma longa L.) and has multiple pharmacological effects. It is mainly found in turmeric and is the main component of turmeric that releases pharmacological activity. Curcumin is active in many fields such as anti-inflammatory, antioxidant and anti-cancer. The efficacy and effects of curcumin generally include improving liver function, lowering blood lipids and anti-cancer. For example, it can be manifested as: 1. Improving liver function: Curcumin can promote the regeneration and repair of liver cells and improve liver function. 2. Lowering blood lipids: Curcumin can lower blood lipid levels, reduce cholesterol deposition, and prevent the occurrence of cardiovascular diseases. 3. Anti-cancer: Curcumin has anti-cancer effects and can prevent the growth and spread of tumors. At the same time, it can also promote the apoptosis of cancer cells. In addition to the above effects, there are also antioxidant and anti-inflammatory effects and functions.

[0005] Although curcumin has a wide range of pharmacological effects, it is poorly absorbed in the body and easily metabolized, so new dosage forms need to be developed to improve its efficacy. Summary of the invention

[0006] The present invention aims to solve one of the technical problems in the related art to at least a certain extent. The present invention provides a colon-localized film coating premix for use in preparing curcumin tablets, which can improve the dissolution of curcumin tablets in the intestine and improve the bioavailability of the drug.

[0007] Specifically, the present invention provides the following technical solutions:

[0008] In a first aspect of the present invention, a colon-specific film coating premix is ​​provided for use in preparing curcumin tablets. The colon-specific film coating premix comprises, in parts by weight:

[0009] 55 to 75 parts by weight of film-forming material,

[0010] 8 to 22 parts by weight of a plasticizer,

[0011] 5 to 15 parts by weight of a colorant,

[0012] 1 to 5 parts by weight of a dispersant,

[0013] 5 to 9 parts by weight of an anti-adhesive agent,

[0014] and 35 to 65 parts by weight of a solvent;

[0015] The film-forming materials include polyacrylic acid resin II, polyacrylic acid resin III, methacrylic acid and methyl methacrylate (1:1) copolymer type A, and methacrylic acid and methyl methacrylate (1:2) copolymer type B.

[0016] According to a specific embodiment, the use of the colon-specific film coating premix mentioned above in the preparation of curcumin tablets may further include the following technical features:

[0017] According to an embodiment of the present invention, the colon-specific film coating premix comprises, in parts by weight:

[0018] 60 to 70 parts by weight of film-forming material,

[0019] 10 to 20 parts by weight of a plasticizer,

[0020] 8 to 12 parts by weight of a colorant,

[0021] 2 to 4 parts by weight of a dispersant,

[0022] 6 to 8 parts by weight of an anti-adhesive agent, and

[0023] 40 to 60 parts by weight of solvent.

[0024] According to an embodiment of the present invention, the mass ratio of the polyacrylic resin II, polyacrylic resin III, methacrylic acid and methyl methacrylate (1:1) copolymer type A, and methacrylic acid and methyl methacrylate (1:2) copolymer type B is 1:(6-8):(1-3):(2-4).

[0025] According to an embodiment of the present invention, the plasticizer is selected from one or more mixtures of polyethylene glycol 4000, triethyl citrate, medium-chain fatty acid triglycerides, and dibutyl sebacate.

[0026] According to an embodiment of the present invention, the colorant is selected from one or more mixtures of iron oxide, titanium dioxide, carmine aluminum lake, fruit green aluminum lake, and lemon yellow aluminum lake.

[0027] According to an embodiment of the present invention, the dispersant is selected from a mixture of one or more of dextrin, sorbitan monopalmitate or Tween 80.

[0028] According to an embodiment of the present invention, the anti-sticking agent is selected from at least one of talc, magnesium stearate and magnesium oxide.

[0029] According to an embodiment of the present invention, the solvent is at least one of ethanol and water.

[0030] The second aspect of the present invention provides a curcumin tablet, comprising: 10 to 12 parts by weight of a colon-specific film coating premix, and 88 to 90 parts by weight of a curcumin bare tablet, wherein the colon-specific film coating premix is ​​coated on the surface of the curcumin bare tablet;

[0031] Wherein, the colon-specific film coating premix comprises, by weight:

[0032] 55 to 75 parts by weight of film-forming material,

[0033] 8 to 22 parts by weight of a plasticizer,

[0034] 5 to 15 parts by weight of a colorant,

[0035] 1 to 5 parts by weight of a dispersant,

[0036] 5 to 9 parts by weight of an anti-adhesive agent,

[0037] and 35 to 65 parts by weight of a solvent;

[0038] The film-forming materials include polyacrylic acid resin II, polyacrylic acid resin III, methacrylic acid and methyl methacrylate (1:1) copolymer type A and methacrylic acid and methyl methacrylate (1:2) copolymer type B.

[0039] According to an embodiment of the present invention, the curcumin tablet provided above may further include the following technical features:

[0040] According to an embodiment of the present invention, the mass ratio of the polyacrylic resin II, polyacrylic resin III, methacrylic acid and methyl methacrylate (1:1) copolymer type A, and methacrylic acid and methyl methacrylate (1:2) copolymer type B is 1:(6-8):(1-3):(2-4).

[0041] According to an embodiment of the present invention, the plasticizer is polyethylene glycol 4000 and triethyl citrate;

[0042] The coloring agents are iron oxide, titanium dioxide and lemon yellow aluminum lake;

[0043] The dispersant is dextrin and Tween 80;

[0044] The anti-sticking agent is talcum powder;

[0045] The solvent is water.

[0046] According to an embodiment of the present invention, the mass ratio of the polyethylene glycol 4000 to triethyl citrate is 2:1, and the mass ratio of the dextrin to the Tween 80 is 1:2.

[0047] The beneficial effects achieved by the present invention are at least:

[0048] The present invention provides a colon-targeted film coating premix, wherein the film-forming material formed by compounding polyacrylic acid resin II, polyacrylic acid resin III, methacrylic acid and methyl methacrylate (1:1) copolymer type A, and methacrylic acid and methyl methacrylate (1:2) copolymer type B can inhibit the drug release rate of the preparation in the stomach, increase the drug release rate in the intestine, control the drug release rate, and improve the drug bioavailability. The film-forming material is matched with a plasticizer, and the release rate of the drug can be further controlled at the same time as the plasticizer, and can be matched with an anti-adhesive agent to prevent adhesion between curcumin particles. The provided colon-targeted film coating premix is ​​used to prepare curcumin tablets, which can improve its bioavailability in the colon, and the sustained release is controllable to ensure the absorption of the drug. DETAILED DESCRIPTION

[0049] Embodiments of the present invention are described in detail below. The embodiments are exemplary and intended to be used to explain the present invention, but should not be construed as limiting the present invention.

[0050] Curcumin has multiple pharmacological and medicinal effects, but its absorption in the body is poor. How to improve its solubility and bioavailability in the body is a problem that needs to be solved. Whether it is through nanoemulsion, nanoparticles, or β-cyclodextrin coating, the process is relatively complicated. During the research process, we chose to prepare curcumin tablets by coating to form a film coating. The process is simple, and the prepared curcumin tablets can be located in the colon for administration, which can reduce its metabolism in the stomach, prolong its release in the colon, and improve its bioavailability in the intestine. However, the selection of a suitable colon-targeted film coating premix is ​​not easy. It needs to combine the physical and chemical properties of different drugs, select suitable polymer materials, and match the auxiliary ingredients to achieve the corresponding purpose.

[0051] The present invention provides a colon-specific film coating premix for use in curcumin tablets. The colon-specific film coating premix comprises, in parts by weight:

[0052] 55 to 75 parts by weight of film-forming material,

[0053] 8 to 22 parts by weight of a plasticizer,

[0054] 5 to 15 parts by weight of a colorant,

[0055] 1 to 5 parts by weight of a dispersant,

[0056] 5 to 9 parts by weight of an anti-adhesive agent,

[0057] and 35 to 65 parts by weight of a solvent;

[0058] The film-forming materials include polyacrylic acid resin II, polyacrylic acid resin III, methacrylic acid and methyl methacrylate (1:1) copolymer type A, and methacrylic acid and methyl methacrylate (1:2) copolymer type B.

[0059] Polypropylene resin II is an anionic methacrylic acid copolymer that is insoluble in gastric juice but soluble in intestinal juice. Polypropylene resin III can be used together with polypropylene resin II. When used for enteric dissolution, it can further increase the flexibility of the film, thereby improving the drug release effect. Methacrylic acid and methyl methacrylate (1:1) copolymer type A is copolymerized by methacrylic acid and methyl methacrylate in a mass ratio of 1:1, and has a high carboxyl to ester ratio. Adding this component can help control the release rate of the drug; methacrylic acid and methyl methacrylate (1:2) copolymer type B is copolymerized by methacrylic acid and methyl methacrylate in a mass ratio of 1:2, and its carboxyl to ester ratio is about 1:2, which can provide a certain viscosity and acidity value, and provide good enteric dissolution performance. The film-forming material formed by compounding these substances can inhibit the drug release rate of the preparation in the stomach, increase the drug release rate in the intestine, control the drug release rate, and improve the bioavailability of the drug. During the research process, it was found that the effect of using several of these film-forming materials alone was not ideal. The film-forming material can be used with the plasticizer used. It can be used as a plasticizer and a pore-forming agent to control the release rate of the drug. It can be used with an anti-adhesive agent to prevent the adhesion between curcumin particles.

[0060] According to a preferred embodiment, the colon-targeted film coating premix comprises, by weight: 65 parts by weight of film-forming material, 15 parts by weight of plasticizer, 10 parts by weight of colorant, 3 parts by weight of dispersant, 7 parts by weight of anti-adherent, and 50 parts by weight of solvent.

[0061] According to a specific embodiment, the mass ratio of the polyacrylic acid resin II, polyacrylic acid resin III, methacrylic acid and methyl methacrylate (1:1) copolymer type A, and methacrylic acid and methyl methacrylate (1:2) copolymer type B is 1:(6-8):(1-3):(2-4). According to a preferred embodiment, the mass ratio of the polyacrylic acid resin II, polyacrylic acid resin III, methacrylic acid and methyl methacrylate (1:1) copolymer type A, and methacrylic acid and methyl methacrylate (1:2) copolymer type B is 1:7:2:3. The film-forming material used can help the drug adapt to disintegration and release in the colon. The plasticizer is selected from one or more mixtures of polyethylene glycol 4000, triethyl citrate, medium-chain fatty acid triglyceride, and dibutyl sebacic acid. According to a preferred embodiment, the plasticizer is polyethylene glycol 4000 and triethyl citrate (preferably in a mass ratio of 2:1). For example, the viscosity of the polyethylene glycol 4000 used is 10.5-16.5mm 2 / s, pH is 6; the relative density of the triethyl citrate used is 1.1389.

[0062] The colorant used is selected from one or more mixtures of iron oxide, titanium dioxide, carmine aluminum lake, fruit green aluminum lake, and lemon yellow aluminum lake.

[0063] The dispersant used is selected from a mixture of one or more of dextrin, sorbitan monopalmitate or Tween 80. According to a preferred embodiment, the dispersant is dextrin and Tween 80. For example, Tween 80 has a relative density of 1.1 and a pH value of 6-8.

[0064] According to a specific embodiment, the anti-sticking agent is selected from at least one of talc, magnesium stearate, and magnesium oxide; for example, the talc used has an average particle size of 4 to 5 μm, a whiteness of 94, a particle size of 50 m, and a sieve residue of 0.1%;

[0065] The technical solution of the present invention is described below by specific examples. It should be noted that these examples are only used to facilitate the understanding of those skilled in the art and should not be regarded as limiting the scope of protection of the present invention. The auxiliary materials used in the examples can all be obtained commercially.

[0066] Example 1

[0067] Example 1 Weigh the ingredients according to Table 1 and mix them evenly to obtain a colon-specific film coating premix.

[0068] Example 2

[0069] Example 2 Weigh the ingredients according to Table 1 and mix them evenly to obtain a colon-specific film coating premix.

[0070] Example 3

[0071] Example 3 Weigh the ingredients according to Table 1 and mix them evenly to obtain a colon-specific film coating premix.

[0072] Comparative Example 1

[0073] Comparative Example 1: The ingredients were weighed according to Table 1 and then mixed evenly to obtain a colon-specific film coating premix.

[0074] Comparative Example 2

[0075] Example 2 Weigh the ingredients according to Table 1 and mix them evenly to obtain a colon-specific film coating premix.

[0076] Comparative Example 3

[0077] Comparative Example 3: The ingredients were weighed according to Table 1 and then mixed evenly to obtain a colon-specific film coating premix.

[0078] Comparative Example 4

[0079] Comparative Example 4: The ingredients were weighed according to Table 1 and then mixed evenly to obtain a colon-targeted film coating premix.

[0080] Comparative Example 5

[0081] Comparative Example 5: The ingredients were weighed according to Table 1 and then mixed evenly to obtain a colon-targeted film coating premix.

[0082] Curcumin bare tablets were used as blank controls, and the curcumin bare tablets only contained curcumin and basic excipients.

[0083] Table 1 Different Examples and Comparative Examples

[0084]

[0085]

[0086] The colon-specific film coating premix prepared in the above embodiments and comparative examples was used to coat the curcumin chips (coating weight gain rate was 10%), with 10 parts by weight of the colon film coating premix and 90 parts by weight of the curcumin chips. The drug release of the prepared coated tablets was investigated.

[0087] Table 2 Drug release of different embodiments and comparative examples is as follows:

[0088]

[0089] At the same time, the appearance of the medicine was investigated, and the results are shown in Table 3 below.

[0090] The appearance of the drugs in different embodiments and comparative examples in Table 3 is as follows:

[0091]

[0092]

[0093] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "examples", and "specific implementation methods" means that the specific features, structures, materials, or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Although the embodiments of the present invention have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be construed as limitations on the present invention. Those of ordinary skill in the art can change, modify, replace, and modify the above embodiments within the scope of the present invention.

Claims

1. Use of a colon-specific film coating premix in the preparation of curcumin tablets, characterized in that: The colon-specific film coating premix comprises, by weight: 55 to 75 parts by weight of film-forming material, 8 to 22 parts by weight of a plasticizer, 5 to 15 parts by weight of a colorant, 1 to 5 parts by weight of a dispersant, 5 to 9 parts by weight of an anti-adhesive agent, and 35 to 65 parts by weight of a solvent; The film-forming materials include polyacrylic acid resin II, polyacrylic acid resin III, methacrylic acid and methyl methacrylate (1:1) copolymer type A and methacrylic acid and methyl methacrylate (1:2) copolymer type B.

2. The use according to claim 1, characterized in that The colon-specific film coating premix comprises, by weight: 60 to 70 parts by weight of film-forming material, 10 to 20 parts by weight of a plasticizer, 8 to 12 parts by weight of a colorant, 2 to 4 parts by weight of a dispersant, 6 to 8 parts by weight of an anti-adhesive agent, and 40 to 60 parts by weight of solvent.

3. The use according to claim 1, characterized in that The mass ratio of the polyacrylic acid resin II, the polyacrylic acid resin III, the methacrylic acid and methyl methacrylate (1:1) copolymer type A, and the methacrylic acid and methyl methacrylate (1:2) copolymer type B is 1: (6-8): (1-3): (2-4).

4. The use according to claim 1, characterized in that The plasticizer is selected from at least one of polyethylene glycol 4000, triethyl citrate, medium chain fatty acid triglyceride, and dibutyl sebacate.

5. The use according to claim 1, characterized in that: The plasticizers are polyethylene glycol 4000 and triethyl citrate.

6. The use according to claim 1, characterized in that: The colorant is selected from at least one of iron oxide, titanium dioxide, carmine aluminum lake, fruit green aluminum lake, and lemon yellow aluminum lake; The dispersant is selected from at least one of dextrin, sorbitan monopalmitate or Tween 80; The anti-sticking agent is selected from at least one of talc, magnesium stearate and magnesium oxide; The solvent is selected from at least one of water and ethanol.

7. A curcumin tablet, characterized in that: include: 10 to 12 parts by weight of a colon-specific film coating premix and 88 to 90 parts by weight of curcumin bare tablets, wherein the colon-specific film coating premix is ​​coated on the surface of the curcumin bare tablets; Wherein, the colon-specific film coating premix comprises, by weight: 55 to 75 parts by weight of film-forming material, 8 to 22 parts by weight of a plasticizer, 5 to 15 parts by weight of a colorant, 1 to 5 parts by weight of a dispersant, 5 to 9 parts by weight of an anti-adhesive agent, and 35 to 65 parts by weight of a solvent; The film-forming materials include polyacrylic acid resin II, polyacrylic acid resin III, methacrylic acid and methyl methacrylate (1:1) copolymer type A and methacrylic acid and methyl methacrylate (1:2) copolymer type B.

8. The curcumin tablet according to claim 7, characterized in that The mass ratio of the polyacrylic acid resin II, the polyacrylic acid resin III, the methacrylic acid and methyl methacrylate (1:1) copolymer type A, and the methacrylic acid and methyl methacrylate (1:2) copolymer type B is 1: (6-8): (1-3): (2-4).

9. The curcumin tablet according to claim 7, characterized in that The plasticizers are polyethylene glycol 4000 and triethyl citrate; The coloring agents are iron oxide, titanium dioxide and lemon yellow aluminum lake; The dispersant is dextrin and Tween 80; The anti-sticking agent is talcum powder; The solvent is water.

10. The curcumin tablet according to claim 9, characterized in that The mass ratio of the polyethylene glycol 4000 to the triethyl citrate is 2:

1. The mass ratio of the dextrin to the Tween 80 is 1:2.

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