Guanxin storax capsule and preparation method thereof

Abstract

The invention provides storax capsules for treating coronary heart disease. The storax capsules are prepared from the following components in parts by weight: 20 to 30 parts of storax, 50 to 55 parts of borneol, 50 to 55 parts of vinegar frankincense, 100 to 120 parts of sandalwood, 100 to 120 parts of elecampane, 0 to 105 parts of starch and 75 to 340 parts of inclusion compound auxiliary materials. The traditional Guanxin storax capsule is subjected to formula and process improvement, the fluidity is improved, the in-vitro dissolution rate is accelerated, the stability is improved, and the preparation method of the Guanxin storax capsule with more advantages is expected to be obtained.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicine preparations, and in particular relates to a Guanxin Suhe capsule and a preparation method thereof. Background Art

[0003] Styrax is a fragrant resin exuded from the trunk of Liquidambar orientalis Mill., a plant of the Hamamelidaceae family. It is an oily liquid, and its main components are cinnamic acid and cinnamic acid esters. It has the effects of opening the mind, eliminating filth, and relieving pain. It can be used to treat stroke, phlegm, sudden collapse, chest pain, heart pain, chest and abdomen cold pain, and epilepsy. Borneol is a crystal made by extracting and processing fresh branches and leaves of Cinnamomum camphora (L.) Presl, a plant of the Lauraceae family. At present, synthetic borneol is mostly used, and its components are borneol and isoborneol. Styrax is pungent and warm, and borneol is pungent and cool. It is aromatic, opens the mind, eliminates filth and turbidity, and relieves depression and pain. It is a monarch drug. Frankincense is a resin exuded from the bark of Boswellia carterii Birdw., a plant of the same genus, Boswellia bhaw-dajiana Birdw., a plant of the Oleaceae family. Its main components are frankincense acids, cedarwood-type diterpenes, etc. Sandalwood is the heartwood of the trunk of Santalum album L., a plant of the Santalaceae family. It is mostly composed of volatile oils, mainly santalol. Frankincense and sandalwood are pungent, warm and dispersing, warm the meridians and activate blood circulation, promote qi and relieve chest tightness, relieve numbness and relieve pain, and are all ministerial drugs. Inula is the dried root of Inula helenium L., a plant of the Asteraceae family. Its main component is lactone components. Inula strengthens the spleen and stomach, promotes qi and relieves pain, and is an adjuvant. All the drugs are used together to achieve the effects of regulating qi and relieving chest tightness, warming the meridians and relieving pain.

[0004] However, the Guanxin Suhe capsules prepared in the prior art have poor fluidity, slow in vitro dissolution rate and low stability. Summary of the invention

[0005] In view of this, the present invention aims to provide a Guanxin Suhe capsule and a preparation method thereof, so as to solve the problems of poor fluidity, slow in vitro dissolution rate and low stability of the Guanxin Suhe capsule.

[0006] To achieve the above object, the technical solution of the present invention is achieved as follows:

[0007] The first aspect of the present invention provides a Guanxin Suhe capsule, comprising the following components in parts by weight: 20-30 parts of storax, 50-55 parts of borneol, 50-55 parts of vinegar frankincense, 100-120 parts of sandalwood, 100-120 parts of inula, 0-105 parts of starch, and 75-340 parts of inclusion compound auxiliary materials.

[0008] Furthermore, the inclusion compound auxiliary material is one or more of β-cyclodextrin (β-CD) and gel-type silicon dioxide.

[0009] Furthermore, the gel-type silica is SYLOID 244FP.

[0010] The second aspect of the present invention provides a method for preparing the Guanxin Suhe capsule according to the first aspect of the present invention, comprising the following steps:

[0011] S1: Grind vinegar frankincense, sandalwood and inula into fine powder, sieve directly or add inclusion compound auxiliary materials and then sieve, mix well to obtain drug powder;

[0012] S2: Mix storax with anhydrous ethanol until it is clear and transparent, add the inclusion compound auxiliary material and stir until it is a powder without lumps to obtain storax powder;

[0013] S3: adding the styrax powder obtained in S2 to the powder in S1, mixing, adding starch slurry, preparing granules, and drying;

[0014] S4: Encapsulate borneol with inclusion compound excipients to prepare borneol inclusion compound, grind into fine powder, mix with the granules obtained in S3, and put into capsules to obtain Guanxin Suhe Capsules.

[0015] Furthermore, the inclusion compound auxiliary material in S1 is SYLOID 244FP, and the mass ratio of the fine powder to SYLOID 244FP is 1:1-5:1.

[0016] Furthermore, the inclusion compound auxiliary material in S2 is SYLOID 244FP, and the mass ratio of styrax to SYLOID 244FP is 1:2-2:1.

[0017] Furthermore, the inclusion compound auxiliary material in S4 is one or more of β-cyclodextrin and gel-type silica, and the inclusion method includes but is not limited to saturated aqueous solution method, spray drying method and direct addition method.

[0018] Furthermore, the borneol content of the borneol inclusion compound in S4 is 5%-60%.

[0019] The third aspect of the present invention provides a method for preparing the Guanxin Suhe capsule according to the first aspect of the present invention, comprising the following steps:

[0020] S1: Grind vinegar frankincense, sandalwood and inula into fine powder, sieve directly or add inclusion compound auxiliary materials and then sieve, mix well to obtain drug powder;

[0021] S2: adding styrax to the powder of S1, mixing, adding starch slurry, making granules, and drying;

[0022] S3: Encapsulate borneol with inclusion compound excipients to prepare borneol inclusion compound, grind into fine powder, mix with the granules obtained in S2, and put into capsules to obtain Guanxin Suhe Capsules.

[0023] Furthermore, the inclusion compound auxiliary material in S1 is SYLOID 244FP, and the mass ratio of the fine powder to SYLOID 244FP is 1:1-5:1.

[0024] Furthermore, the inclusion compound auxiliary material in S3 is one or more of β-cyclodextrin and gel-type silica, and the inclusion method includes but is not limited to saturated aqueous solution method, spray drying method and direct addition method.

[0025] Furthermore, the borneol content of the borneol inclusion compound in S3 is 5%-60%.

[0026] The fourth aspect of the present invention provides the use of inclusion compound excipients in the preparation of Guanxin Suhe capsules, wherein the inclusion compound excipients are one or more of β-cyclodextrin and gel-type silica, and the gel-type silica is SYLOID 244FP.

[0027] Compared with the prior art, the Guanxin Suhe capsule and the preparation method thereof described in the present invention have the following advantages:

[0028] The Guanxin Suhe capsule prepared by the method of the present invention can not only improve its fluidity, accelerate its in vitro dissolution rate, but also improve its stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The accompanying drawings constituting a part of the present invention are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the accompanying drawings:

[0030] Figure 1 The particle size analysis diagram of the borneol inclusion compound described in Experimental Example 2 of the present invention (A: β-CD borneol inclusion compound; B: SYLOID 244FP borneol inclusion compound);

[0031] Figure 2 This is a flowability analysis diagram of the borneol described in Experimental Example 3 of the present invention;

[0032] Figure 3 This is a flowability analysis diagram of the β-CD borneol inclusion compound described in Experimental Example 3 of the present invention;

[0033] Figure 4 This is a flowability analysis diagram of the SYLOID 244FP borneol inclusion compound described in Test Example 3 of the present invention;

[0034] Figure 5 This is a flowability analysis chart of the Guanxin Suhe original prescription described in Test Example 3 of the present invention;

[0035] Figure 6 This is a flowability analysis diagram of the Guanxin Suhe-β-CD borneol inclusion complex described in Experimental Example 3 of the present invention;

[0036] Figure 7 This is a flowability analysis diagram of the Guanxin Suhe-SYLOID 244FP borneol inclusion complex described in Test Example 3 of the present invention;

[0037] Figure 8 The dissolution curve of borneol and borneol inclusion compound described in Test Example 4 of the present invention;

[0038] Fig. 9 The dissolution curves of the original and improved Guanxin Suhe prescriptions described in Test Example 4 of the present invention;

[0039] Fig.10 FT-IR spectra of the gel-type silica, borneol, physical mixture, and borneol inclusion compound described in Test Example 6 of the present invention;

[0040] Fig.11 The DSC spectra of the gel-type silica, borneol, physical mixture, and borneol inclusion compound described in Test Example 6 of the present invention (Note: 1: borneol; 2: gel-type silica; 3: gel-type silica inclusion compound; 4: gel-type silica-borneol physical mixture);

[0041] Fig.12 The SEM images of the gel-type silica, borneol, physical mixture, and borneol inclusion compound described in Test Example 6 of the present invention (Note: A, C: gel-type silica; B, D: gel-type silica borneol inclusion compound);

[0042] Fig.13 TGA spectra of gel-type silica, borneol, physical mixture, and borneol inclusion complex described in Test Example 6 of the present invention (Note: A: gel-type silica; B: synthetic borneol; C: SYLOID 244FP borneol inclusion complex). DETAILED DESCRIPTION

[0043] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments may be combined with each other.

[0044] The present invention will be described in detail below with reference to the accompanying drawings and in conjunction with embodiments.

[0045] Example 1

[0046] A Guanxin Suhe capsule comprises the following components in parts by weight: styrax, borneol, vinegar frankincense, sandalwood, inulin, starch and inclusion compound auxiliary materials. In terms of weight percentage, the dosage of each component is as follows: 7.0% styrax, 14.0% borneol, 14.0% vinegar frankincense, 28.0% sandalwood, 28.0% inulin, 9.3% SYLOID 244FP and 2.8% starch.

[0047] The preparation method of the Guanxin Suhe capsule comprises the following steps:

[0048] S1: Grind vinegar frankincense, sandalwood and inula into fine powder, mix well, and obtain medicinal powder;

[0049] S2: Mix storax with anhydrous ethanol until it becomes clear and transparent to obtain storax ethanol solution;

[0050] S3: adding the styrax ethanol solution obtained in S2 to the powder in S1, mixing, adding starch slurry, preparing granules, and drying;

[0051] S4: Add borneol dissolved in anhydrous ethanol to SYLOID 244FP, stir for 20 minutes, and dry to obtain borneol inclusion compound. Grind the borneol inclusion compound into fine powder, mix it with the granules obtained in S3, and put it into capsules to obtain Guanxin Suhe Capsules.

[0052] Example 2

[0053] A Guanxin Suhe capsule comprises the following components in parts by weight: styrax, borneol, vinegar frankincense, sandalwood, inulin, starch and inclusion compound auxiliary materials. In terms of weight percentage, the dosage of each component is as follows: 3.8% styrax, 7.9% borneol, 7.9% vinegar frankincense, 15.8% sandalwood, 15.8% inulin, 1.5% starch and 47.3% beta-cyclodextrin.

[0054] The preparation method of the Guanxin Suhe capsule comprises the following steps:

[0055] S1: Grind vinegar frankincense, sandalwood and inula into fine powder, mix well, and obtain medicinal powder;

[0056] S2: Mix storax with anhydrous ethanol until it becomes clear and transparent to obtain storax ethanol solution;

[0057] S3: adding the styrax ethanol solution obtained in S2 to the powder in S1, mixing, adding starch slurry, preparing granules, and drying;

[0058] S4: Add borneol dissolved in anhydrous ethanol to a saturated aqueous solution of β-cyclodextrin, stir for 2 hours, filter, wash and dry to obtain borneol inclusion compound, crush the borneol inclusion compound into fine powder, mix it with the granules obtained in S3, and put it into capsules to obtain Guanxin Suhe Capsules.

[0059] Example 3

[0060] A Guanxin Suhe capsule comprises the following components in parts by weight: styrax, borneol, vinegar frankincense, sandalwood, inulin, starch and inclusion compound auxiliary materials. In terms of weight percentage, the dosage of each component is as follows: 3.5% styrax, 7.4% borneol, 7.4% vinegar frankincense, 14.8% sandalwood, 14.8% inulin, 7.4% SYLOID 244FP and 44.5% beta-cyclodextrin.

[0061] The preparation method of the Guanxin Suhe capsule comprises the following steps:

[0062] S1: Grind vinegar frankincense, sandalwood and inula into fine powder, add SYLOID 244FP, sieve and mix well to obtain powder; the mass ratio of fine powder to SYLOID 244FP is 5:1;

[0063] S2: adding styrax to the powder of S1, mixing, adding starch slurry, making granules, and drying;

[0064] S3: Add borneol dissolved in anhydrous ethanol to a saturated aqueous solution of β-cyclodextrin, stir for 2 hours, filter, wash and dry to obtain borneol inclusion compound, crush the borneol inclusion compound into fine powder, mix it with the granules obtained in S3, and put it into capsules to obtain Guanxin Suhe Capsules.

[0065] Comparative Example 1

[0066] A Guanxin Suhe capsule comprises the following components in parts by weight: styrax, borneol, vinegar frankincense, sandalwood, inula, and starch. In terms of weight percentage, the dosage of each component is as follows: 4.6% styrax, 9.6% borneol, 9.6% vinegar frankincense, 19.1% sandalwood, 19.1% inula, and 37.9% starch.

[0067] The preparation method of the Guanxin Suhe capsule comprises the following steps:

[0068] S1: Grind vinegar frankincense, sandalwood and inula into fine powder, add starch, sieve and mix well to obtain medicinal powder; the mass ratio of the fine powder to starch is 5:2;

[0069] S2: Mix storax with anhydrous ethanol until it is clear and transparent, add starch, and stir until it is a powder without lumps to obtain storax powder; the mass ratio of storax to starch is 1:1;

[0070] S3: adding the styrax powder obtained in S2 to the powder in S1, mixing, adding starch slurry, preparing granules, and drying;

[0071] S4: Add appropriate amount of starch to borneol, crush into fine powder, mix with the granules obtained in S3, and put into capsules to obtain Guanxin Suhe Capsules.

[0072] Test Example 1: Properties and Content Comparison Test

[0073] (1) Experimental method: Take appropriate amounts of the powders in the Guanxin Suhe capsules of Example 1 and Comparative Example 1, and identify the properties of the powders in terms of color, smell, texture, etc. The content of borneol in the powders is determined by gas chromatography, and the method for determining the content is as follows:

[0074] A gas chromatography separation / non-separation injection port and a flame ionization detection system are used, with 6% cyanopropylbenzene and 94% dimethylsiloxane as the stationary phase, and the temperature control system adopts a program temperature rise: after maintaining 70°C for 2 minutes, it is raised to 150°C at a rate of 40°C / min, and then raised to 190°C at a rate of 4°C / min, and maintained for 2 minutes. The flow rate is 2.0mL / min. The theoretical plate number should not be less than 18000 calculated according to the borneol peak. Preparation of reference solution: accurately weigh appropriate amounts of borneol and methyl salicylate reference substances, add anhydrous ethanol to make a solution containing 0.5mg per 1mL, accurately measure appropriate amounts of each, mix, and prepare a reference solution for correction factor determination; preparation of test solution: take 100mg of the dry powder of Guanxin Suhe Capsule of the present invention, add 10mL of anhydrous ethanol to dissolve and inject; determination method: gas chromatography, accurately aspirate 1μL of reference solution and test solution respectively, inject into gas chromatograph, and determine.

[0075] (2) Experimental results: The powder of Example 1 is lighter in color, lighter in texture, and less bitter than the powder of Comparative Example 1. The results of borneol content are shown in Table 1.

[0076] Table 1 Content of borneol in samples of Example 1 and Comparative Example 1

[0077]

[0078]

[0079] Test Example 2 Particle Size Analysis

[0080] The SYLOID 244FP borneol inclusion complex and β-CD borneol inclusion complex in Example 1 and Example 2 were subjected to particle size analysis. 90% of the β-CD borneol inclusion complex had a particle size less than 5.70 μm, and 99% of the β-CD borneol inclusion complex had a particle size less than 8.37 μm; 90% of the SYLOID 244FP borneol inclusion complex had a particle size less than 4.27 μm, and 99% of the SYLOID 244FP borneol inclusion complex had a particle size less than 6.48 μm.

[0081] Test Example 3 Fluidity Analysis

[0082] The slope can reflect the dynamic friction coefficient between powder particles. The larger the slope, the larger the friction coefficient, and the worse the fluidity of the powder; the bulk density can be used to characterize the fluidity of powder blends. The SYLOID244FP borneol inclusion complex and β-CD borneol inclusion complex and preparations in Example 1 and Example 2 were taken for fluidity analysis. As shown in Table 2, the fluidity of borneol can be enhanced after inclusion by β-CD and SYLOID 244FP; however, the fluidity of the Guanxinsuhe-β-CD borneol inclusion complex is better than that of the Guanxinsuhe original formula and the Guanxinsuhe-SYLOID 244FP borneol inclusion complex, which may be because the amount of β-CD used is 5-6 times that of other preparations, indicating that the fluidity of the preparation depends not only on the type of excipients, but also on the amount of excipients used.

[0083] Table 2 Slope and bulk density of borneol, borneol inclusion compound and preparation

[0084]

[0085] Test Example 4 In vitro dissolution study

[0086] The SYLOID 244FP borneol inclusion compound and β-CD borneol inclusion compound and the preparation in Example 1 and Example 2 were subjected to in vitro dissolution test. Figure 8 As shown, the cumulative dissolution rates of SYLOID 244FP borneol inclusion complex and β-CD borneol inclusion complex were higher than that of borneol, indicating that the in vitro dissolution rate of borneol was significantly improved after inclusion with SYLOID 244FP and β-CD, and the inclusion effect of SYLOID244FP was better than that of β-CD. Fig. 9 The results showed that the in vitro dissolution rate of the improved formula of Guanxin Suhe Borneol inclusion complex was better than that of the original formula of Guanxin Suhe, which further verified the above results.

[0087] Test Example 5 Accelerated Stability Investigation

[0088] The accelerated stability experiments of borneol, borneol inclusion complexes and preparations showed that the borneol content of borneol and SYLOID 244FP borneol inclusion complexes decreased by nearly 100% on the 14th day under the conditions of 40°C and 75% relative humidity. In contrast, the borneol content of β-CD borneol inclusion complexes was only about 5%, indicating that the stability of borneol can be significantly improved after β-CD inclusion, while there is no gain effect after SYLOID 244FP inclusion.

[0089] Table 3 Accelerated stability results of borneol, borneol inclusion compound and preparation

[0090]

[0091] Test Example 6 Characterization and Identification of Borneol Inclusion Compound

[0092] FT-IR: Take appropriate amount of gel-type silica, borneol, physical mixture, and borneol inclusion compound powder respectively, and use KBr tablet method to measure infrared spectrum. Test range: 400-4000cm -1 .

[0093] FT-IR analysis: FT-IR spectra of gel-type silica, borneol, physical mixture, and borneol inclusion complex are shown in Fig.10 As shown in the spectrum of the gel-type silica borneol inclusion complex, there is right-handed borneol at 2924 cm -1 The stretching vibration peak of 1400-1000cm -1 The peaks in the interval all disappeared, indicating that the characteristic peaks were shielded by gel-type silica, which also confirmed the formation of a new phase. Although the spectra of physical mixtures have a similar trend, there are cases where the wave numbers of characteristic peaks such as O-Si-O are not completely equal.

[0094] DSC: Take appropriate amounts of gel-type silica, borneol, physical mixture, and borneol inclusion compound powders, place them in an aluminum pan, adjust the temperature, increase the temperature at a rate of 10°C / min, and perform differential calorimetry scanning in the range of 30-500°C.

[0095] DSC analysis: The thermodynamic effects of the four substances can be obtained through differential scanning calorimetry analysis. Fig.11 It can be seen that in the spectrum of gel-type silica inclusion complex, the small absorption peak at 45℃-55℃ may be the absorption peak of synthetic borneol, and there are two absorption peaks at 168℃-230℃, which is similar to the spectrum of physical mixture, indicating that borneol is more inclined to be in a state of simple mixing and adsorption into the cavity of SYLOID 244FP.

[0096] SEM: SEM analysis was performed on gel-type silica and borneol inclusion complex respectively.

[0097] SEM analysis: The surface morphology of gel-type silica and gel-type silica-borneol inclusion complex was observed using a scanning electron microscope. Fig.12 It can be seen that the gel-type silica is in the form of small balls aggregated together. Borneol is a colorless, transparent or white, flaky, crisp crystal. The gel-type silica-borneol inclusion complex does not have the crystal structure of borneol, indicating that borneol may exist in the cavity of the gel-type silica.

[0098] TGA: Take appropriate amount of gel-type silica, borneol, physical mixture, and borneol inclusion compound powder respectively, put them into a thermogravimetric analyzer for thermogravimetric measurement. The measurement conditions are: temperature range 0-400℃, heating rate 10℃ / min, nitrogen flow rate 30mL / min.

[0099] TGA analysis: Thermogravimetric analysis is a method to study the thermodynamics of different samples after thermal degradation and can evaluate the thermal stability of different samples. Fig.13 It can be seen that the temperature and thermogravimetric curve of SYLOID 244FP properties remain basically unchanged, and the weight decreases by 4%. The synthetic borneol is completely volatilized before 150°C and the weight becomes 0. The weight of SYLOID 244FP borneol inclusion complex also decreases by about 50% before 150°C, and then the weight remains stable, indicating that the synthetic borneol inside is volatilized and is not completely encapsulated.

[0100] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A Guanxin Suhe capsule, characterized in that: The invention comprises the following components in parts by weight: 20-30 parts of storax, 50-55 parts of borneol, 50-55 parts of vinegar frankincense, 100-120 parts of sandalwood, 100-120 parts of inula, 0-105 parts of starch and 75-340 parts of inclusion compound auxiliary materials.

2. The Guanxin Suhe capsule according to claim 1, characterized in that: The inclusion compound auxiliary material is one or more of beta-cyclodextrin and gel-type silicon dioxide.

3. The Guanxin Suhe capsule according to claim 2, characterized in that: The gel-type silica is SYLOID 244FP.

4. A method for preparing Guanxin Suhe Capsule according to any one of claims 1 to 3, characterized in that: The following steps are involved: S1: Grind vinegar frankincense, sandalwood and inula into fine powder, sieve directly or add inclusion compound auxiliary materials and then sieve, mix well to obtain drug powder; S2: Mix storax with anhydrous ethanol until it is clear and transparent, add the inclusion compound auxiliary material and stir until it is a powder without lumps to obtain storax powder; S3: adding the styrax powder obtained in S2 to the powder in S1, mixing, adding starch slurry, preparing granules, and drying; S4: Encapsulate borneol with inclusion compound excipients to prepare borneol inclusion compound, grind into fine powder, mix with the granules obtained in S3, and put into capsules to obtain Guanxin Suhe Capsules.

5. A method for preparing Guanxin Suhe Capsule according to any one of claims 1 to 3, characterized in that: The following steps are involved: S1: Grind vinegar frankincense, sandalwood and inula into fine powder, sieve directly or add inclusion compound auxiliary materials and then sieve, mix well to obtain drug powder; S2: adding styrax to the powder of S1, mixing, adding starch slurry, making granules, and drying; S3: Encapsulate borneol with inclusion compound excipients to prepare borneol inclusion compound, grind into fine powder, mix with the granules obtained in S2, and put into capsules to obtain Guanxin Suhe Capsules.

6. The method for preparing Guanxin Suhe Capsule according to claim 4 or 5, characterized in that: The inclusion compound auxiliary material in S1 is SYLOID 244FP, and the mass ratio of fine powder to SYLOID 244FP is 1:1-5:

1.

7. The method for preparing Guanxin Suhe Capsule according to claim 4, characterized in that: The inclusion compound auxiliary material in S2 is SYLOID 244FP, and the mass ratio of styrax to SYLOID 244FP is 1:2-2:

1.

8. The method for preparing Guanxin Suhe Capsule according to claim 4 or 5, characterized in that: The inclusion compound auxiliary material of the borneol inclusion compound is one or more of β-cyclodextrin and gel-type silicon dioxide, and the inclusion method includes but is not limited to a saturated aqueous solution method, a spray drying method and a direct addition method.

9. The method for preparing Guanxin Suhe Capsule according to claim 4 or 5, characterized in that: The borneol content of the borneol inclusion compound is 5%-60%.

10. Application of inclusion compound auxiliary materials in the preparation of Guanxin Suhe capsules, characterized in that: The inclusion compound excipients are one or more of β-cyclodextrin and gel-type silicon dioxide; The gel-type silica is SYLOID 244FP.

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