Glucosamine calcium tablet preparation and preparation method thereof

Abstract

The invention discloses a glucosamine calcium tablet preparation and a preparation method thereof. The glucosamine calcium tablet preparation comprises 4-6 parts of active composite particles, 0.2-0.3 part of L-calcium ascorbate, 3.5-5.5 parts of sodium alginate, 1-2 parts of water-soluble inorganic calcium, 5-6 parts of cellulose ether and 1.5-2.5 parts of a plasticizer. The active composite particles are chitosan-chondroitin sulfate micro-capsules containing glucosamine salt; the cellulose ether and the plasticizer form a coating layer. The water resistance and oxidation resistance of the glucosamine calcium tablet preparation are improved, and the effective dose, the drug effect duration and the glucosamine utilization rate of the glucosamine calcium tablet preparation are also improved.

Description

Technical Field

[0001] The present invention relates to a glucosamine calcium tablet preparation and a preparation method thereof, belonging to the technical field of glucosamine preparations. Background Art

[0002] Glucosamine, a natural amino monosaccharide, is an essential substance for synthesizing proteoglycans in the matrix of human articular cartilage. Glucosamine participates in the metabolism of the human body and is widely used in the treatment of arthritis, regulation of the body's immune function, antioxidant and other aspects.

[0003] At present, glucosamine products include tablets, capsules, oral liquids, etc. They enter the human body through oral administration, are digested and absorbed, and participate in the metabolism of the human body. The common glucosamine product is the tablet form. Generally, the glucosamine core is coated. However, due to the large pores in the ordinary drug coating, the sealing and waterproof properties are average. And because of the poor chemical properties of glucosamine, the glucosamine tablets are deliquesced and oxidized by air, resulting in a reduction in the effective drug loading of the glucosamine tablets; in addition, it also causes the glucosamine tablets to be rapidly released after entering the human body, forming an excessively high glucosamine concentration, which cannot be fully absorbed and utilized, and will also cause irritation to the stomach, resulting in a short duration of drug effect and a reduction in the utilization rate of glucosamine. Summary of the Invention

[0004] At least aiming at one of the above problems existing in the prior art, the present invention provides a glucosamine calcium tablet preparation and a preparation method thereof. The glucosamine calcium tablet preparation adopts the same functions of microcapsule-crosslinked network layer-coating layer to improve the waterproof and antioxidant properties of the glucosamine calcium tablet preparation, and also improves the effective drug amount, duration of drug effect and utilization rate of glucosamine of the glucosamine calcium tablet preparation.

[0005] In order to achieve the above object, the present invention adopts the following technical scheme: A glucosamine calcium tablet preparation, comprising the following raw materials and parts by weight: 4-6 parts of active composite particles, 0.2-0.3 part of L-ascorbic acid calcium, 3.5-5.5 parts of sodium alginate, 1-2 parts of water-soluble inorganic calcium, 5-6 parts of cellulose ether and 1.5-2.5 parts of plasticizer;

[0006] The active composite particles are chitosan-chondroitin sulfate microcapsules containing glucosamine salts.

[0007] The cellulose ether and the plasticizer form a coating layer.

[0008] Preferably, in the glucosamine calcium tablet preparation, the active composite particles, L-ascorbic acid calcium and sodium alginate are mixed, and are successively coated with water-soluble inorganic calcium and the coating layer.

[0009] Preferably, the glucosamine salt is one of glucosamine sulfate or glucosamine hydrochloride, and glucosamine sulfate is preferred.

[0010] Preferably, the water-soluble inorganic calcium is one of calcium chloride or calcium sulfate.

[0011] Preferably, the plasticizer is one of polyethylene glycol or triacetin.

[0012] Preferably, the cellulose ether is selected from one of carboxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose or ethyl cellulose.

[0013] Preferably, the preparation process of the active composite particles is as follows:

[0014] (1) Form a mixed aqueous phase from chitosan and chondroitin sulfate.

[0015] (2) Form a W / O emulsion from the glucosamine salt, ethyl acetate and composite emulsifier.

[0016] (3) Add the mixed aqueous phase to the W / O emulsion, add sodium tripolyphosphate after stirring is completed, stir at a temperature of 45 - 52 °C, and then separate, wash and dry to obtain.

[0017] Preferably, the composite emulsifier is composed of a mixture of lecithin and span 80.

[0018] Preferably, the mass ratio of the glucosamine salt, chitosan and chondroitin sulfate is 1:4 - 4.5:0.4 - 0.6.

[0019] Preferably, the specific preparation method of the active composite particles is as follows:

[0020] (1) After fully mixing a 2% acetic acid solution of chitosan and a 0.2% chondroitin sulfate solution, form a mixed aqueous phase.

[0021] (2) Fully mix ethyl acetate and the composite emulsifier to form an emulsion, and then add an 8 - 25% aqueous solution of glucosamine salt and stir at a high speed of 1200 - 1500 rpm to form a W / O emulsion.

[0022] (3) Slowly add the mixed aqueous phase from step (1) to the W / O emulsion in step (2) in portions within 1.5 h. After the addition is completed, continue to stir for 1 - 1.5 h, add a 12.5% aqueous solution of sodium tripolyphosphate, stir at a temperature of 45 - 52 °C for 2.5 - 3 h, then filter with suction for separation, wash with ethanol, and dry in vacuum to obtain chitosan - chondroitin sulfate microcapsules containing glucosamine salt.

[0023] Preferably, the volume ratio of the aqueous solution of glucosamine salt to the emulsion is 1:3 - 4.

[0024] Preferably, in the emulsion, the mass fraction of the composite emulsifier is 1.75%.

[0025] Preferably, the composite emulsifier is formed by mixing lecithin and Span 80 in a mass ratio of 2.5:1.

[0026] Preferably, the mass ratio of sodium tripolyphosphate to chitosan is 1:1.5.

[0027] Preferably, the concentration of acetic acid in the acetic acid solution is 1%.

[0028] The present invention also provides a preparation method of a glucosamine calcium tablet preparation, comprising the following steps:

[0029] S1. Mix 4 - 6 parts of active composite particles, 0.1 - 0.2 part of L-ascorbic acid calcium, and 3.5 - 5.5 parts of sodium alginate evenly, add water to form a paste and then granulate to form mixed particles;

[0030] S2. Dissolve 1 - 2 parts of water-soluble inorganic calcium in an aqueous ethanol solution of 75% to form an inorganic calcium solution with a mass fraction of 20 - 25%, then spray the inorganic calcium solution onto the rolling mixed particles in step S1, and then roll and dry to form a core;

[0031] S3. Dissolve 5 - 6 parts of cellulose ether and 1.5 - 2.5 parts of plasticizer in water to form a coating solution, and then coat the core in step S2 with the coating solution, and dry to form a film to obtain the glucosamine calcium tablet preparation.

[0032] Preferably, in step S2, the inorganic calcium concentration of the inorganic calcium solution is 20 - 25%.

[0033] Preferably, in step S3, the mass concentration of the coating solution is 25 - 30%.

[0034] Advantages of the present invention: The glucosamine calcium tablet preparation of the present invention belongs to the manufacture of biological drugs. It uses chitosan - chondroitin sulfate microcapsules containing glucosamine salts, which are mixed with sodium alginate to form granules, and then inorganic calcium is sprayed. The calcium ions form a cross - linked network layer with sodium alginate. The synergy between the microcapsules and the cross - linked network layer endows the glucosamine calcium tablet preparation with balanced sustained - release properties. Then, it is coated. In this way, the interaction of the microcapsule - cross - linked network layer - coating layer improves the waterproof and antioxidant properties of the glucosamine calcium tablet preparation, thereby enhancing the effective drug dose, the duration of drug efficacy, and the utilization rate of glucosamine in the glucosamine calcium tablet preparation; in the glucosamine calcium tablet preparation of the present invention, there is a cross - linked network layer formed by calcium ions and sodium alginate between the microcapsules and the coating, which can synergistically promote the balanced sustained - release of glucosamine salts with the microcapsules, and the calcium ions in the cross - linked network layer contribute to the supplement of calcium elements after digestion and absorption; the glucosamine calcium tablet preparation of the present invention prepares chitosan - chondroitin sulfate microcapsules containing glucosamine salts, which have good effective drug loading capacity and encapsulation efficiency, and have good sustained - release properties, thereby promoting the duration of drug efficacy; the glucosamine calcium tablet preparation of the present invention uses calcium L - ascorbate. In addition to supplementing calcium, it can further prevent the oxidation of glucosamine and promote the increase of the effective drug dose of glucosamine; in the process of preparing chitosan - chondroitin sulfate microcapsules containing glucosamine salts in the glucosamine calcium tablet preparation of the present invention, lecithin and span are used to form a composite emulsifier, and sodium tripolyphosphate is used as a cross - linker, which helps to improve the effective drug loading capacity and encapsulation efficiency of the microcapsules, with small and uniform particle size and good dispersibility; in addition, lecithin has good biocompatibility, is soluble in water, and forms a strong binding strength with the microcapsules, which helps the sustained - release absorption of glucosamine. Detailed implementation manners

[0035] The following is a clear and complete description of the technical solutions in the implementation of the present invention. The described embodiments are only a part of the embodiments of the present invention, rather than all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention. For those not specified in the embodiments, the conventional conditions or the conditions recommended by the manufacturer are followed. For the reagents, instruments, or components not specified for the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0036] Example 1

[0037] A glucosamine calcium tablet preparation and its preparation method, the preparation steps are as follows:

[0038] Step 1: Preparation of active composite particles:

[0039] Step 1.1, thoroughly mixing a 2% (w / w) chitosan acetic acid solution (acetic acid concentration is 1% (w / w)) and a 0.2% (w / w) chondroitin sulfate solution to form a mixed aqueous phase;

[0040] Step 1.2, ethyl acetate and a composite emulsifier prepared by mixing lecithin and Span 80 in a mass ratio of 2.5:1 are thoroughly mixed to form an emulsion containing 1.75% (w / w) of the composite emulsifier, and a 20% (w / w) aqueous solution of glucosamine sulfate is added and stirred at a high speed of 1200-1500 rpm. The volume ratio of the glucosamine sulfate solution to the emulsion is 1:4 to form a W / O emulsion;

[0041] Step 1.3, slowly adding the mixed aqueous phase of step (1) to the W / O emulsion of step (2) in portions within 1.5 hours, with the mass ratio of glucosamine sulfate, chitosan, and chondroitin sulfate being 1:4:0.5. After the addition is completed, stirring is continued for 1 hour, and a 12.5% sodium tripolyphosphate aqueous solution is added, with the mass ratio of sodium polyphosphate to chitosan being 1:1.5. The temperature is controlled at 48°C, stirred for 2.5 hours, then filtered and separated, washed with ethanol, and vacuum dried to obtain chitosan-chondroitin sulfate microcapsules containing glucosamine sulfate, i.e., micro-active composite particles;

[0042] Step 2: Evenly mix 5 parts of the active composite particles prepared in step 1, 0.25 parts of calcium L-ascorbate, and 4.5 parts of sodium alginate, add water to form a paste, and then granulate to form mixed particles;

[0043] Step 3, dissolving 1.5 parts of calcium chloride in a 75% ethanol aqueous solution to form an inorganic calcium solution with an inorganic calcium concentration of 23% (w / w), spraying the inorganic calcium solution onto the rolling mixed particles of step 2, and then rolling and drying to form an inner core;

[0044] Step 4: dissolve 5.5 parts of carboxymethyl cellulose and 2 parts of polyethylene glycol in water to form a coating solution with a mass concentration of 28%, then coat the inner core of step 3 with the coating solution, dry it into a film, and obtain a glucosamine calcium tablet preparation.

[0045] Example 2

[0046] A glucosamine calcium tablet preparation and a preparation method thereof, the preparation steps are as follows:

[0047] Step 1: Preparation of active composite particles is the same as in Example 1;

[0048] Step 2: Evenly mix 4 parts of the active composite particles prepared in step 1, 0.2 parts of calcium L-ascorbate, and 3.5 parts of sodium alginate, add water to form a paste, and then granulate to form mixed particles;

[0049] Step 3: Dissolve 1 part of calcium chloride in an aqueous solution of 75% ethanol to form an inorganic calcium solution with an inorganic calcium concentration of 20% (w / w). Then spray the inorganic calcium solution onto the rolling mixed particles in Step 2, and then roll and dry to form the inner core;

[0050] Step 4: Dissolve 5 parts of carboxymethyl cellulose and 1.5 parts of polyethylene glycol in water to form a coating solution with a mass concentration of 25%. Then coat the inner core in Step 3 with the coating solution and dry to form a film, obtaining the glucosamine calcium tablet preparation.

[0051] Example 3

[0052] A glucosamine calcium tablet preparation and its preparation method are as follows:

[0053] Step 1: The preparation of the active composite particles is the same as in Example 1;

[0054] Step 2: Mix 6 parts of the active composite particles in Step 1, 0.3 part of calcium L-ascorbate, and 5.5 parts of sodium alginate evenly, add water to form a paste and then granulate to form mixed particles;

[0055] Step 3: Dissolve 2 parts of calcium sulfate in an aqueous solution of 75% ethanol to form an inorganic calcium solution with an inorganic calcium concentration of 25% (w / w). Then spray the inorganic calcium solution onto the rolling mixed particles in Step 2, and then roll and dry to form the inner core;

[0056] Step 4: Dissolve 6 parts of carboxymethyl cellulose and 2.5 parts of polyethylene glycol in water to form a coating solution with a mass concentration of 30%. Then coat the inner core in Step 3 with the coating solution and dry to form a film, obtaining the glucosamine calcium tablet preparation.

[0057] Example 4

[0058] A glucosamine calcium tablet preparation and its preparation method are as follows:

[0059] Step 1: The preparation of the active composite particles is the same as in Example 1;

[0060] Step 2: Mix 6 parts of the active composite particles in Step 1, 0.2 part of calcium L-ascorbate, and 3.5 parts of sodium alginate evenly, add water to form a paste and then granulate to form mixed particles;

[0061] Step 3: Dissolve 1 part of calcium sulfate in an aqueous solution of 75% ethanol to form an inorganic calcium solution with an inorganic calcium concentration of 20% (w / w). Then spray the inorganic calcium solution onto the rolling mixed particles in Step 2, and then roll and dry to form the inner core;

[0062] Step 4: Dissolve 5 parts of carboxymethyl cellulose and 1.5 parts of polyethylene glycol in water to form a coating solution with a mass concentration of 25%. Then coat the core obtained in Step 3 with the coating solution and dry it to form a film, obtaining the glucosamine calcium tablet preparation.

[0063] Example 5

[0064] A glucosamine calcium tablet preparation and its preparation method are as follows:

[0065] Step 1: Preparation of active composite particles:

[0066] Step 1.1: After fully mixing a 2% (w / w) chitosan acetic acid solution (acetic acid concentration is 1% (w / w)) and a 0.2% (w / w) chondroitin sulfate solution, form a mixed aqueous phase;

[0067] Step 1.2: Fully mix ethyl acetate and a composite emulsifier composed of lecithin and span 80 in a mass ratio of 2.5:1 to form an emulsion containing 1.75% (w / w) composite emulsifier. Then add a 25% (w / w) glucosamine sulfate aqueous solution and stir at a high speed of 1200 - 1500 rpm. The volume ratio of the glucosamine sulfate aqueous solution to the emulsion is 1:3.5 to form a W / O emulsion;

[0068] Step 1.3: Gradually and slowly add the mixed aqueous phase obtained in Step (1) to the W / O emulsion in Step (2) within 1.5 h. The mass ratio of glucosamine salt, chitosan, and chondroitin sulfate is 1:4.5:0.6. After the addition is completed, continue to stir for 1.2 h. Then add a 12.5% sodium tripolyphosphate aqueous solution. The mass ratio of sodium polyphosphate to chitosan is 1:1.5. Control the temperature at 45°C and stir for 2.8 h. Then filter by suction, wash with ethanol, and dry in vacuum to obtain chitosan - chondroitin sulfate microcapsules containing glucosamine sulfate, that is, micro - active composite particles;

[0069] The remaining steps are the same as those in Example 1.

[0070] Example 6

[0071] A glucosamine calcium tablet preparation and its preparation method are as follows:

[0072] Step 1: Preparation of active composite particles:

[0073] Step 1.1: After fully mixing a 2% (w / w) chitosan acetic acid solution (acetic acid concentration is 1% (w / w)) and a 0.2% (w / w) chondroitin sulfate solution, form a mixed aqueous phase;

[0074] Step 1.1: Thoroughly mix ethyl acetate and a composite emulsifier composed of lecithin and span 80 in a mass ratio of 2.5:1 to form an emulsion containing 1.75% (w / w) of the composite emulsifier. Then add 15% (w / w) of an aqueous glucosamine sulfate solution and stir at a high speed of 1200 - 1500 rpm. The volume ratio of the aqueous glucosamine sulfate solution to the emulsion is 1:3 to form a W / O emulsion.

[0075] Step 1.1: Gradually and slowly add the mixed aqueous phase from Step (1) to the W / O emulsion from Step (2) within 1.5 h. The mass ratio of glucosamine salt, chitosan, and chondroitin sulfate is 1:4.25:0.4. After the addition is complete, continue stirring for 1.5 h. Then add a 12.5% aqueous sodium tripolyphosphate solution. The mass ratio of sodium polyphosphate to chitosan is 1:1.5. Control the temperature at 52°C and stir for 3 h. Then perform suction filtration separation, wash with ethanol, and dry in vacuum to obtain chitosan-chondroitin sulfate microcapsules containing glucosamine sulfate, i.e., microactive composite particles.

[0076] The remaining steps are the same as those in Example 1.

[0077] Comparative Example 1

[0078] A glucosamine calcium tablet preparation and its preparation method are as follows:

[0079] Step 1: Mix 0.91 parts of glucosamine sulfate, 3.64 parts of chitosan, 0.45 parts of chondroitin sulfate, 0.2 - 0.3 parts of L-ascorbic acid calcium, and 3.5 - 5.5 parts of sodium alginate evenly. Add water to form a paste and then granulate to form mixed granules.

[0080] Step 2: Dissolve 1.5 parts of calcium chloride in an aqueous ethanol solution of 75% to form an inorganic calcium solution with an inorganic calcium concentration of 23% (w / w). Then spray the inorganic calcium solution onto the rolling mixed granules from Step 2, and then roll and dry to form the core.

[0081] Step 3: Dissolve 5.5 parts of carboxymethyl cellulose and 2 parts of polyethylene glycol in water to form a coating solution with a mass concentration of 28%. Then coat the core from Step 3 with the coating solution and dry to form a film to obtain the glucosamine calcium tablet preparation.

[0082] Comparative Example 2

[0083] A glucosamine calcium tablet preparation and its preparation method, which are different from those in Example 1 in that amino acid chelated calcium is used instead of L-ascorbic acid calcium.

[0084] Comparative Example 3

[0085] A glucosamine calcium tablet preparation and its preparation method are as follows:

[0086] Step 1: The preparation of the active composite particles is the same as in Example 1;

[0087] Step 2: Mix 5 parts of the active composite particles from Step 1, 0.25 part of calcium L-ascorbate, 4.5 parts of sodium alginate, and 1.5 parts of calcium chloride evenly, add water to form a paste, and then granulate to form mixed particles;

[0088] Step 3: Dissolve 5.5 parts of carboxymethyl cellulose and 2 parts of polyethylene glycol in water to form a coating solution with a mass concentration of 28%, and then coat the core from Step 3 with the coating solution and dry to form a film to obtain the glucosamine calcium tablet preparation.

[0089] Comparative Example 4

[0090] A glucosamine calcium tablet preparation and its preparation method, which are different from Example 1 in that: in the preparation of the active composite particles: the temperature in Step 1.3 is 40°C; the rest is the same as in Example 1.

[0091] Comparative Example 5

[0092] A glucosamine calcium tablet preparation and its preparation method, which are different from Example 1 in that: in the preparation of the active composite particles: the temperature in Step 1.3 is 55°C; the rest is the same as in Example 1.

[0093] Comparative Example 6

[0094] A glucosamine calcium tablet preparation and its preparation method, which are different from Example 1 in that: in the preparation of the active composite particles: the mixed aqueous phase is only a 2% (w / w) acetic acid solution of chitosan (acetic acid concentration is 1% (w / w)), and the mass ratio of glucosamine sulfate to chitosan is 1:4.5; the rest is the same as in Example 1.

[0095] Comparative Example 7

[0096] A glucosamine calcium tablet preparation and its preparation method, which are different from Example 1 in that: in the preparation of the active composite particles: the mass ratio of glucosamine salt, chitosan, and chondroitin sulfate is 1:3.5:0.5.

[0097] Comparative Example 8

[0098] A glucosamine calcium tablet preparation and its preparation method, which are different from Example 1 in that: in the preparation of the active composite particles: the mass ratio of glucosamine salt, chitosan, and chondroitin sulfate is 1:5:0.5.

[0099] Comparative Example 9

[0100] A glucosamine calcium tablet preparation and its preparation method, which are different from Example 1 in that: glutaraldehyde is used instead of sodium tripolyphosphate.

[0101] Comparative Example 10

[0102] A glucosamine calcium tablet preparation and its preparation method, which are different from Example 1 in that: in the preparation of active composite microparticles: the composite emulsifier only contains lecithin.

[0103] Comparative Example 11

[0104] A glucosamine calcium tablet preparation and its preparation method, which are different from Example 1 in that: in the preparation of active composite microparticles: the emulsifier is composed of Span 80 and magnesium stearate mixed in a mass ratio of 1.5:0.5, and the emulsion contains 1.5% (w / w) of the composite emulsifier; the rest is the same as Example 1.

[0105] Performance test:

[0106] 1. The particle size, dispersibility, encapsulation rate and drug loading of the active composite microparticles of Example 1, Examples 5 - 6 and Comparative Examples 4 - 11 were measured; the results are shown in Table 1.

[0107] Table 1

[0108]

[0109]

[0110] From Table 1 above, among the active composite particles prepared in Example 1, Example 5 and Example 6 of the present invention, they have better encapsulation of the active ingredient glucosamine salt, and at the same time have good drug loading capacity. The active composite particles have smaller particle size and better particle size dispersion uniformity; compared with Comparative Example 4 and Comparative Example 5, the temperature of 45-52 °C in Example 1, Example 5 and Example 6 is more suitable, which is beneficial to improving the encapsulation rate of glucosamine salt, making the active composite particles more spherical, not sticky, and obtaining smaller particle size and better dispersion uniformity; compared with Comparative Example 6, chondroitin sulfate is added in Example 1. Chondroitin sulfate acts synergistically with chitosan, which can improve the encapsulation rate of glucosamine salt, increase the drug loading capacity, and also improve the particle size and dispersion uniformity of the active composite particles; compared with Comparative Example 7 and Comparative Example 8, the mass ratio of glucosamine salt, chitosan, and chondroitin sulfate in Example 1, Example 5 and Example 6 in the range of 1:4-4.5:0.4-0.6 is more suitable, which helps to improve the encapsulation rate and drug loading capacity of glucosamine salt, makes the active composite particles more spherical, and improves the particle size and dispersion uniformity of the active composite particles; compared with Comparative Example 9, sodium tripolyphosphate is used as a crosslinking agent in Example 1 when preparing chitosan-chondroitin sulfate microcapsules containing glucosamine salt, which helps to improve the encapsulation rate and drug loading capacity of glucosamine salt, and also greatly improves the dispersion uniformity of the particle size of the composite particles; compared with Comparative Example 10 and Comparative Example 11, a composite emulsifier formed by lecithin and span is used in Example 1 when preparing chitosan-chondroitin sulfate microcapsules containing glucosamine salt, which can promote the encapsulation rate and drug loading capacity of glucosamine salt, and improve the particle size and dispersion uniformity of the active composite particles.

[0111] 2. For the glucosamine calcium tablet preparations of Examples 1-6 and the glucosamine calcium tablet preparations of Comparative Examples 1-11, the content change of glucosamine in a sealed box with an oxygen concentration of 35% was measured after being placed for 1 day, 4 days, 8 days, 14 days, 21 days, and 30 days respectively. The measurement method was RP-HPL derivatization method. Taking the glucosamine salt content in the glucosamine calcium tablet preparation before testing as the initial amount, the proportion of the content on other days relative to the initial amount was calculated. The results are shown in Table 2.

[0112] Table 2

[0113]

[0114] As can be seen from Table 2 above, compared with Comparative Example 1 and Comparative Example 3, the glucosamine tablets of Example 1 use chitosan-chondroitin sulfate microcapsules and a coating layer containing glucosamine salts, and there is a cross-linked network layer formed by calcium ions and sodium alginate between the microcapsules and the coating. The synergistic effect of the microcapsule-cross-linked network layer-coating layer has good antioxidant properties. Compared with Comparative Example 2, calcium L-ascorbate is used in Example 1, which further enhances the antioxidant property of glucosamine, promotes the increase of the effective drug amount of glucosamine, and can also supplement calcium at the same time; combined with Table 1, it is also found from Examples 1 to 6 and Comparative Examples 4 to 11 that the high encapsulation rate of the microcapsules can also prevent the further oxidation of glucosamine.

[0115] 3. The moisture absorption rates of the glucosamine calcium tablet preparations of Examples 1 to 6 and the glucosamine calcium tablet preparations of Comparative Examples 1 to 11 were measured, and the results are shown in Table 3.

[0116]

[0117]

[0118] As can be seen from Table 3 above, compared with Comparative Example 1 and Comparative Example 3, the glucosamine tablets of Example 1 have a lower deliquescence rate. They use chitosan-chondroitin sulfate microcapsules and a coating layer containing glucosamine salts, and there is a cross-linked network layer formed by calcium ions and sodium alginate between the microcapsules and the coating. The synergistic effect of the microcapsule-cross-linked network layer-coating layer has good waterproof and air-permeability prevention performance, and also helps the sustained-release absorption of the preparation and the supplementation of calcium elements in the human body.

[0119] 4. The in vitro glucosamine dissolution rates of the glucosamine calcium tablet preparations of Examples 1 to 6 and the glucosamine calcium tablet preparations of Comparative Examples 1, 3, and 7 to 9 were tested, and the results are shown in Table 4 below.

[0120] Table 4

[0121]

[0122] As can be seen from Table 4 above, the glucosamine calcium tablet preparations of Examples 1 to 6 have good sustained-release effects, maintaining a longer drug efficacy duration; the initial dissolution rate is low, which helps to reduce the irritation to the stomach; and they can be completely sustained-released within 24 hours. The dissolution rate within the first 12 hours is less than 80%, and the dissolution rate in each time period is relatively balanced. The remaining drug amount is dissolved within the subsequent 12 hours and is relatively balanced. This can not only enable the full absorption of glucosamine, improve the utilization rate of glucosamine, but also reduce the dosage and frequency. Compared with Comparative Example 1, the active composite particles used in the glucosamine calcium tablet preparation of Example 1 are chitosan-chondroitin sulfate microcapsules containing glucosamine salts, and this microcapsule structure can enhance the sustained-release effect of glucosamine salts; compared with Comparative Example 3, the glucosamine calcium tablet preparation of Example 1 has a cross-linked network layer formed by calcium ions and sodium alginate between the microcapsules and the coating, which can synergistically promote the balanced sustained-release of glucosamine salts with the microcapsules, making the preparation have the performance of balanced sustained-release. In addition, combining Table 1, it is found from Examples 1, Comparative Example 7, Comparative Example 8, and Comparative Example 9 that the higher the encapsulation rate of the chitosan-chondroitin sulfate microcapsules containing glucosamine salts, the slower the release of glucosamine salts and the better the sustained-release effect; and compared with Comparative Example 11, the cumulative dissolution of glucosamine in Comparative Example 7 is slowed down. It is found from the preparation of the active composite particles in Examples 1, Comparative Example 7, and Comparative Example 11 that the composite emulsifiers in Example 1 and Comparative Example 7 contain lecithin. Perhaps because of the good biocompatibility of lecithin and its solubility in water, it will form a strong binding strength with the microcapsules, making the active composite particles contain lecithin and improving the sustained-release effect of glucosamine.

[0123] 5. Take the glucosamine calcium tablet preparations of Example 1 and Comparative Example 6, and select white rats with osteoarticular diseases as the experimental subjects. Example 1 and Comparative Example 1 correspond to a group of white rats with osteoarticular diseases, with 15 white rats with osteoarticular diseases in each group. They are continuously administered twice a day (once every 12 hours), one tablet each time. During this period, the white rats are allowed to eat and drink freely; continuous administration for 4 weeks completes one course of treatment; observe the healing situation, marked effect, and effective rate; observe and sacrifice the white rats 24 hours later, take out the intestines and observe the mucosal phenomenon, where the effective rate = (healing + marked effect) / the total number of this group, as shown in Table 5.

[0124] Table 5

[0125]

[0126] As can be seen from Table 5 above, compared with Comparative Example 6, the active composite particles used in the glucosamine calcium tablet preparation of Example 1 contain chondroitin sulfate, which can promote the absorption and utilization of glucosamine, and glucosamine and chondroitin sulfate work synergistically to make the preparation have a better therapeutic effect on osteoarthritis; in addition, glucosamine and chondroitin sulfate synergistically promote intestinal mucosa repair and improve intestinal mucosa integrity; compared with Comparative Example 11, combined with Table 4, in the preparation of the active composite particles of Example 1, the composite emulsifier contains lecithin, which will form a strong binding strength with the microcapsules, so that the active composite particles contain lecithin, which helps the absorption and utilization of glucosamine and increases the therapeutic effect.

[0127] For those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and the present invention can be implemented in other specific forms without departing from the spirit and basic characteristics of the present invention. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-limiting. The scope of the present invention is defined by the appended claims rather than the above description. Therefore, all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be included in the present invention.

[0128] In addition, it should be understood that although this specification is described according to embodiments, not every embodiment only contains an independent technical solution. This narrative way of the specification is only for clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A glucosamine calcium tablet preparation, characterized in that, It includes the following raw materials and parts by weight: 4 - 6 parts of active composite microparticles, 0.2 - 0.3 part of L - calcium ascorbate, 3.5 - 5.5 parts of sodium alginate, 1 - 2 parts of water - soluble inorganic calcium, 5 - 6 parts of cellulose ether and 1.5 - 2.5 parts of plasticizer; The active composite microparticles are chitosan - chondroitin sulfate microcapsules containing glucosamine salts; The cellulose ether and the plasticizer form a coating layer.

2. The glucosamine calcium tablet preparation according to claim 1, wherein The glucosamine salt is one of glucosamine sulfate or glucosamine hydrochloride.

3. The glucosamine calcium tablet preparation according to claim 1, wherein The water - soluble inorganic calcium is one of calcium chloride or calcium sulfate; the plasticizer is one of polyethylene glycol or triacetin; the cellulose ether is selected from one of carboxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose or ethyl cellulose.

4. A glucosamine calcium tablet preparation according to claim 1, characterized in that, The preparation process of the active composite microparticles: (1) Form a mixed aqueous phase from chitosan and chondroitin sulfate; (2) Form a W / O emulsion from glucosamine salt, ethyl acetate and composite emulsifier; (3) Add the mixed aqueous phase to the W / O emulsion, add sodium tripolyphosphate after stirring is completed, stir at a temperature of 45 - 52 °C, and then separate, wash and dry to obtain.

5. A glucosamine calcium tablet preparation according to claim 4, characterized in that, The composite emulsifier is composed of lecithin and Span 80 mixed.

6. The glucosamine calcium tablet preparation according to claim 5, characterized in that, The composite emulsifier is composed of lecithin and Span 80 mixed according to a mass ratio of 2.5:

1.

7. A glucosamine calcium tablet preparation according to claim 4, characterized in that, The mass ratio of glucosamine salt, chitosan and chondroitin sulfate is 1:4 - 4.5:0.4 - 0.

6.

8. A glucosamine calcium tablet preparation according to any one of claims 4 to 7, characterized in that The specific preparation method of the active composite microparticles is as follows: (1) After fully mixing a 2% acetic acid solution of chitosan and a 0.2% chondroitin sulfate solution, form a mixed aqueous phase; (2) Fully mix ethyl acetate and the composite emulsifier to form an emulsion, and then add an 8 - 25% aqueous solution of glucosamine salt and stir at a high speed of 1200 - 1500 rpm to form a W / O emulsion; (3) Slowly add the mixed aqueous phase in step (1) to the W / O emulsion in step (2) in portions within 1.5 h. After the addition is completed, continue to stir for 1 - 1.5 h, add a 12.5% aqueous solution of sodium tripolyphosphate, stir at a temperature of 45 - 52 °C for 2.5 - 3 h, then filter with suction to separate, wash with ethanol, and dry in vacuum to obtain chitosan - chondroitin sulfate microcapsules containing glucosamine salt.

9. A glucosamine calcium tablet preparation according to claim 8, characterized in that, The volume ratio of the aqueous solution of glucosamine salt to the emulsion is 1:3 - 4; in the emulsion, the mass fraction of the composite emulsifier is 1.75%; the mass ratio of sodium tripolyphosphate to chitosan is 1:1.

5.

10. A preparation method of the glucosamine calcium tablet preparation according to claim 1, characterized in that, It includes the following steps: S1. Mix 4 - 6 parts of active composite microparticles, 0.1 - 0.2 part of L - calcium ascorbate and 3.5 - 5.5 parts of sodium alginate evenly, add water to form a paste and then granulate to form mixed particles; S2. Dissolve 1 - 2 parts of water - soluble inorganic calcium in a 75% aqueous ethanol solution to form an inorganic calcium solution with a mass fraction of 20 - 25%, and then spray the inorganic calcium solution onto the rolling mixed particles in step S1, and then roll and dry to form an inner core; S3. Dissolve 5 - 6 parts of cellulose ether and 1.5 - 2.5 parts of plasticizer in water to form a coating solution, and then coat the inner core in step S2 with the coating solution and dry to form a film to obtain the glucosamine calcium tablet preparation.

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