Pharmaceutical composition containing abelmoschus manihot extract as well as preparation method, preparation and application of pharmaceutical composition

Abstract

The invention discloses a pharmaceutical composition containing an abelmoschus manihot flower extract and a preparation method, application and a preparation thereof, and belongs to the technical field of pharmaceutical preparations, the pharmaceutical composition is composed of the abelmoschus manihot flower extract, magnesium stearate and calcium hydrogen phosphate. Compared with the prior art, the pharmaceutical composition disclosed by the invention has better long-term stability, and the medicament prepared by applying the pharmaceutical composition is smaller in volume, so that the taking discomfort or swallowing difficulty of a patient is reduced, and the compliance is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to a pharmaceutical composition containing a hibiscus flower extract, and a preparation method, a preparation and an application thereof. Background Art

[0002] Medicinal Hibiscus flower is the dried corolla of Abelmoschus manihot (L.) Medic, a plant of the Malvaceae family. It tastes sweet and cold, and enters the kidney and bladder meridians. It has the effects of clearing dampness and heat, reducing swelling and detoxifying, and is used for carbuncle swelling, toxicity, and burns caused by water or fire. This medicine was first recorded in "Jiayou Materia Medica", which records: Hibiscus flower is used to treat all kinds of malignant sores and pus that have not healed for a long time, and it can be applied as powder. "Compendium of Materia Medica" says: Hibiscus flower, its flower smell is sweet, cold, slippery, and non-toxic. It can treat all kinds of malignant sores and pus that have not healed for a long time, and it can be cured by applying it as powder, which is an important medicine for sores.

[0003] Prior art CN102600219A provides a hibiscus flower extract, and its preparation forms include capsules, tablets, etc., wherein the capsule prescription is: hibiscus flower total flavonoids extract 400g, hydroxypropyl cellulose 20g, talcum powder 15g, microcrystalline cellulose 20g, calcium sulfate 20g, a total of 1000 capsules, each capsule of the invention contains 475mg of content, wherein the auxiliary material is 75mg. Prior art CN1994337A provides a hibiscus flower total flavonoids capsule, and its prescription is hibiscus flower total flavonoids extract 5-100g, starch 125g, granulated with an appropriate amount of 75% ethanol to make a total of 1000 capsules, and also provides a hibiscus flower total flavonoids tablet, the prescription is: hibiscus flower total flavonoids extract 1-100g, dextrin 90g, microcrystalline cellulose 105g, low-substituted hydroxypropyl methylcellulose 15g, 70% ethanol 15ml, magnesium stearate 1g. Considering that magnesium stearate is mainly used as a lubricant in the production of capsules and tablets, and the concentration used is 0.25%-0.5% (W / W), more other excipients are needed. The existing technology contains more excipients, which will make the tablets larger for tablets, and for capsules, larger capsule shells such as No. 0 capsules are needed for filling, which may cause some patients to report a foreign body sensation or difficulty in swallowing after swallowing.

[0004] Therefore, it is necessary to provide a formulation with less pharmaceutical excipients so as to be suitable for making smaller tablets or filling in smaller sizes such as No. 1 capsules, so as to reduce patient discomfort or difficulty in swallowing, improve compliance, and achieve drug standards that meet pharmacopoeia standards. Summary of the invention

[0005] The object of the present invention is to provide a pharmaceutical composition containing hibiscus flower extract and a preparation method, preparation and application thereof. The present invention utilizes magnesium stearate and calcium hydrogen phosphate in a specific ratio to improve the hygroscopicity of hibiscus flower extract, reduce the proportion of excipients in the content, effectively achieve a smaller preparation volume, reduce the patient's discomfort or difficulty in swallowing, and improve compliance.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a pharmaceutical composition containing hibiscus flower extract, which is composed of hibiscus flower extract, magnesium stearate and calcium hydrogen phosphate.

[0008] The mass ratio of the hibiscus flower extract, magnesium stearate and calcium hydrogen phosphate is 400:19-22:8-12; preferably 400:19-22:9-11; further preferably 400:19-22:10; and most preferably 400:20:10.

[0009] In a second aspect, the present invention provides a method for preparing the pharmaceutical composition, comprising the following steps:

[0010] (1) wet-granulating the formulated amount of hibiscus flower extract and calcium hydrogen phosphate to obtain mixed granules;

[0011] (2) uniformly mixing the mixed granules obtained in step (1) and the formulated amount of magnesium stearate.

[0012] The binder used in the wet granulation of the present invention is ethanol, preferably 55-80 v / v% ethanol; more preferably 60-80 v / v% ethanol; more preferably 60-75 v / v% ethanol.

[0013] The pharmaceutical composition of the present invention is in the form of capsules, tablets or granules, and can be prepared by different preparation methods according to the actual dosage form.

[0014] In a third aspect, the present invention provides a method for improving the stability of a hibiscus flower extract.

[0015] The method comprises: adjusting the mass ratio of hibiscus flower extract, magnesium stearate and calcium hydrogen phosphate to 400:19-22:8-12; preferably 400:19-22:9-11; more preferably 400:19-22:10; and most preferably 400:20:10.

[0016] In a fourth aspect, the present invention provides use of the above-mentioned pharmaceutical composition or the above-mentioned method in the preparation of a hibiscus flower extract preparation.

[0017] The preparation is in the form of capsules, tablets or granules.

[0018] In a fifth aspect, the present invention provides a preparation containing a hibiscus flower extract, wherein the preparation is prepared from the above-mentioned pharmaceutical composition or the method.

[0019] The preparation is capsule, tablet or granule.

[0020] The hibiscus flower extract involved in the present invention is an ethanol extract of hibiscus flower.

[0021] Specifically, the preparation method of the hibiscus flower extract comprises the following steps: adding ethanol to the hibiscus flower and heating and refluxing to extract the hibiscus flower extract.

[0022] Preferably, the volume percentage of the ethanol is 90-98%, more preferably 92-98%, more preferably 92-95%, and even more preferably 95%.

[0023] Preferably, the amount of ethanol added is 15-20 times the mass of the hibiscus flower, more preferably 16-20 times, more preferably 17-19 times; and even more preferably 18 times.

[0024] Preferably, the reflux time is 0.5-3 hours, more preferably 0.5-2.5 hours, more preferably 0.5-2 hours, and even more preferably 1 hour.

[0025] Preferably, the method for preparing the Hibiscus tiliaceus flower extract comprises the following steps:

[0026] (1) adding ethanol to hibiscus flowers, heating under reflux, filtering, and obtaining a filtrate;

[0027] (2) concentrating the obtained filtrate under reduced pressure to obtain a concentrated solution;

[0028] (3) Adjust the pH value of the concentrate, refrigerate and let stand, remove the oil layer, dry and grind to obtain the concentrate.

[0029] Further preferably, the volume percentage of ethanol in step (1) is 90-98%; further preferably 92-98%, further preferably 92-95%, and even more preferably 95%.

[0030] Further preferably, the amount of ethanol added in step (1) is 15-20 times the mass of hibiscus flowers; further preferably 16-20 times, further preferably 17-19 times; and further preferably 18 times.

[0031] More preferably, the reflux time in step (1) is 0.5-3 hours; more preferably 0.5-2.5 hours, more preferably 0.5-2 hours, and even more preferably 1 hour.

[0032] Further preferably, the reduced pressure concentration in step (2) is to concentrate to a relative density of 1.10-1.25 (50°C), further preferably 1.12-1.25 (50°C); further preferably 1.12-1.23 (50°C) and further preferably 1.20 (50°C).

[0033] Further preferably, the pH value in step (3) is 5.8-7; further preferably 6-7; further preferably 6-6.8; and further preferably 6.

[0034] More preferably, the refrigerated standing in step (3) is: standing at -4-4°C for 24-48 hours; more preferably standing at 0-4°C for 24-48 hours; and even more preferably standing at 0-4°C for 24 hours.

[0035] The beneficial effects of the present invention are:

[0036] (1) The present invention uses magnesium stearate and calcium hydrogen phosphate in a specific ratio to improve the hygroscopicity of the hibiscus flower extract, reduce the proportion of excipients in the content, and effectively achieve a smaller volume of the preparation. Compared with the prior art, the preparation prepared using the pharmaceutical composition of the present invention has a smaller volume, reduces the patient's discomfort or difficulty in swallowing, and improves compliance.

[0037] (2) The preparation prepared using the pharmaceutical composition of the present invention has good disintegration performance and stability and can meet the requirements of the pharmacopoeia.

[0038] (3) Compared with the prior art, the pharmaceutical composition containing hibiscus flower extract and the preparation thereof of the present invention have better long-term stability. DETAILED DESCRIPTION

[0039] The following examples are only used to help understand the method of the present invention and its core idea. It should be noted that for those of ordinary skill in the art, without departing from the principles of the present invention, the present invention may also be subjected to several improvements and modifications, which also fall within the scope of protection of the claims of the present invention. The following description of the disclosed embodiments enables professionals and technicians in this field to implement or use the present invention. It will be apparent to professionals and technicians in this field that various modifications to these embodiments, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but may be applied to a wider range consistent with the principles and novel features disclosed herein. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those of ordinary skill in the art to which the present invention belongs.

[0040] The following are examples and comparative examples of the present invention, and the pharmaceutical composition, preparation and method for improving the stability of the hibiscus flower extract of the present invention are described in more detail, but the present invention is not limited thereto.

[0041] The present invention does not limit the sources of the raw materials used. Unless otherwise specified, the raw materials used in the present invention are all common commercial products in the technical field. The specific raw material information is shown in Table 1.

[0042] Table 1 Raw material information

[0043]

[0044] The size parameters of the No. 1 gelatin hollow capsule in the embodiment are: locking length 20.4±0.3mm, outer diameter body 6.60mm, outer diameter cap 6.90mm, capsule volume 0.54mm 3 The size parameters of the size 0 gelatin hollow capsule in the present invention are: locking length 21.7±0.3mm, outer diameter body 7.34mm, outer diameter cap 7.64mm, capsule volume 0.68mm 3 .

[0045] Example 1 Preparation of Hibiscus tiliaceus Flower Extract

[0046] Example 1-1 Preparation of Hibiscus tiliaceus Flower Extract

[0047] Take 2000g of hibiscus flower, add 18 times the amount of 95% ethanol, heat and reflux for 1 hour, filter, reduce the pressure of the filtrate to recover ethanol, concentrate to a relative density of 1.20, adjust the pH value of the concentrate to 6.0, stand at 0-4°C for 24 hours, remove the oil layer of the refrigerated solution, vacuum dry, and crush to obtain a hibiscus flower extract with a moisture content of less than 4%.

[0048] Example 1-2 Preparation of Hibiscus tiliaceus Flower Extract

[0049] Take 2000g of hibiscus flower, add 15 times the amount of 90% ethanol, heat and reflux for 2 hours, filter, reduce the pressure of the filtrate to recover ethanol, concentrate to a relative density of 1.10, adjust the pH value of the concentrate to 6.5, stand at 0-4°C for 24 hours, remove the oil layer of the refrigerated solution, vacuum dry, and crush to obtain a hibiscus flower extract with a moisture content of less than 4%.

[0050] Example 1-3 Preparation of Hibiscus tiliaceus Flower Extract

[0051] Take 2000g of hibiscus flower, add 20 times the amount of 98% ethanol, heat and reflux for 3 hours, filter, reduce the pressure of the filtrate to recover ethanol, concentrate to a relative density of 1.25, adjust the pH value of the concentrate to 7.0, stand at 0-4°C for 48 hours, remove the oil layer of the refrigerated solution, vacuum dry, and crush to obtain a hibiscus flower extract with a moisture content of less than 4%.

[0052] Example 1-4 Preparation of Hibiscus tiliaceus Flower Extract

[0053] Take 2000g of hibiscus flower, add 18 times the amount of 90% ethanol, heat and reflux for 1 hour, filter, reduce the pressure of the filtrate to recover ethanol, concentrate to a relative density of 1.20, adjust the pH value of the concentrate to 6.3, stand at 0-4°C for 48 hours, remove the oil layer of the refrigerated solution, vacuum dry, and crush to obtain a hibiscus flower extract with a moisture content of less than 4%.

[0054] Example 2 Investigation and Study on the Pharmaceutical Composition Containing Hibiscus Mallow Flower Extract

[0055] The prescription of the pharmaceutical composition containing the Hibiscus tiliaceus flower extract is shown in Table 2.

[0056] Table 2 Prescription of the pharmaceutical composition containing Hibiscus tiliaceus flower extract (1000 capsules, calculated per capsule)

[0057] Prescription Number Hibiscus tiliaceus flower extract / g Magnesium stearate / g Calcium hydrogen phosphate / g Total weight / g Z1 400 15 85 500 Z2 400 15 65 480 Z3 400 15 45 460 Z4 400 15 25 440 Z5 400 15 5 420 Z6 400 20 5 425 Z7 400 20 10 430 Z8 400 20 15 435

[0058] The preparation method of the pharmaceutical composition is as follows: according to the prescription in Table 2 (wherein the hibiscus flower extract is prepared by using Example 1-1), the hibiscus flower extract and calcium hydrogen phosphate are placed in a mixer, the mixture is started for 5 minutes, an appropriate amount of 70% ethanol is added to prepare a soft material, granulated with a 20-mesh sieve, dried at 70°C, and granulated with an 18-mesh sieve.

[0059] The granules were added into a V-type mixer and magnesium stearate was added, and mixed at a speed of 15-30 r / min for 5-10 min to obtain the corresponding pharmaceutical compositions Z1-Z8.

[0060] The bulk density was investigated with reference to the bulk density determination method of GB / T 33810-2017. The pharmaceutical composition sample was placed on a white paper, and the intermediate sample was smoothly and slowly slid into a 100 mL measuring cylinder at an angle of about 45°. The surface of the pharmaceutical composition sample was gently flattened, and the measuring cylinder was not shaken. The volume was measured, and the mass m of the pharmaceutical composition sample was weighed. The sample was raised by 25 mm and dropped onto a rubber base pad. This was repeated 50 times, and the volume V was measured and recorded. The actual density ρactual=m / v was calculated. Each pharmaceutical composition sample was measured 3 times, and the average value was taken. The measurement results are shown in Table 3.

[0061] Table 3 Bulk density measurement results and corresponding volumes of different prescription drug compositions

[0062] Prescription Number Theoretical prescription amount (g / tablet) Theoretical volume (ml / particle) ρ real (g, ml) Z1 0.50 0.5466 0.9184 Z2 0.48 0.5261 0.9123 Z3 0.46 0.5073 0.9068 Z4 0.44 0.4963 0.8866 Z5 0.42 0.4736 0.8869 Z6 0.425 0.4623 0.9193 Z7 0.43 0.4583 0.9382 Z8 0.435 0.4515 0.9634

[0063] From Table 3, it can be seen that the theoretical volume of each capsule of each prescription is between 0.4515-0.5466ml, because the volume of the No. 1 gelatin empty capsule is 0.54ml. According to the Chinese Pharmacopoeia 2015 Edition, Part IV (General Principle 0103), the difference in the filling volume of Chinese medicine hard capsules under the capsule item is controlled within ±10%. Considering the weight fluctuation of the contents during the mass production filling process, the volume of the contents shall not be greater than 0.4909ml. Therefore, only the prescriptions of the drug composition Z5-Z8 can be filled into the No. 1 gelatin empty capsule.

[0064] The sample filling process of the pharmaceutical composition Z7 was investigated for filling volume differences (theoretical filling volume is 0.430 g / tablet). The results are shown in Table 4.

[0065] Table 4: The amount of the pharmaceutical composition Z7 prescription capsules filled at different time periods

[0066]

[0067]

[0068] According to the requirements of the fourth general rules of the 2015 edition of the Chinese Pharmacopoeia, the range of the difference in the amount of capsules is 0.387-0.473g. From Table 4, the maximum weight is 0.444g, the minimum is 0.408g, the average is 0.422g, the RSD is less than 2%, and the fluctuation is very small. The difference in the amount of filling meets the requirements of the fourth part of the 2015 edition of the Chinese Pharmacopoeia, and the filling is stable.

[0069] The sample filling process of the pharmaceutical composition Z8 was investigated for filling volume differences (theoretical filling volume is 0.430 g / tablet). The results are shown in Table 5.

[0070] Table 5: The amount of the pharmaceutical composition Z8 prescription capsules filled at different time periods

[0071]

[0072]

[0073] As shown in Table 5, the filling amount of the pharmaceutical composition Z8 was stable with small fluctuations at the initial stage of the filling process, but fluctuated greatly at 11 minutes, with the RSD% exceeding 3%.

[0074] The pharmaceutical composition was subjected to the filling, aluminum-plastic and pillow-packing processes of No. 0 (T1 prescription) and No. 1 gelatin empty capsules (other prescriptions). The properties of each group of samples were examined at a temperature of 40±2°C and a relative humidity of 75±5%. The results are shown in Table 6.

[0075] Table 6 Characteristic inspection table at different time periods

[0076]

[0077] It can be seen from Table 6 that the prescriptions of drug compositions Z5 and Z6 have lumps and are difficult to disperse when accelerated for 6 months, and the properties are not ideal. The prescription properties of drug compositions Z7 and Z8 are consistent with drug composition Z1.

[0078] Example 3 Long-term stability study of a pharmaceutical composition containing a Hibiscus truncatum flower extract

[0079] The pharmaceutical composition containing the hibiscus flower extract was prepared into capsules, and the prescription was shown in Table 7. The hibiscus flower extract in each prescription was prepared according to the method of Example 1-1.

[0080] Table 7 Prescription of the pharmaceutical composition containing Hibiscus tiliaceus flower extract (1000 capsules, calculated per capsule)

[0081] Prescription Number Hibiscus tiliaceus flower extract / g Magnesium stearate / g Calcium hydrogen phosphate / g Total weight / g Z1 400 15 85 500 Z5 400 15 5 420 Z7 400 20 10 430 Z8 400 20 15 435

[0082] The preparation method is as follows: according to the prescription in Table 7 (wherein the hibiscus flower extract is prepared according to Example 1-1), the hibiscus flower extract and calcium hydrogen phosphate are placed in a mixer, the mixture is started for 5 minutes, an appropriate amount of 70% ethanol is added to prepare a soft material, granulated with a 20-mesh sieve, dried at 70° C., granulated with 18-mesh sieves, the granules are added to a V-type mixer, magnesium stearate is added, and the mixture is mixed at a speed of 15-30 r / min for 5-10 minutes to obtain an intermediate;

[0083] The intermediate obtained by the total blending was filled, aluminum-plastic, and pillow-packed using a capsule machine (model NJP-3800). Z1 used No. 1 gelatin hollow capsules. Others used No. 0 gelatin hollow capsules. After filling, the semi-finished products were examined for differences in filling volume, moisture content, and disintegration time. The long-term stability of the capsules packaged in aluminum-plastic packaging was studied.

[0084] The filling volume difference (theoretical filling volume is 0.430g / capsule) during the filling process was investigated. According to the requirements of the Chinese Pharmacopoeia 2015 Edition Part IV (General Rules for Preparations 0103) for capsules [Filling Volume Difference], the allowable fluctuation range is ±10%, that is, the filling volume range is 0.387g-0.473g. The results showed that the fluctuation range of the Z7 prescription in different time periods was within ±10%, and the RSD was less than 2%. The filling volume difference met the requirements of the Chinese Pharmacopoeia 2015 Edition Part IV, and the filling volume was stable.

[0085] Place at a temperature of 25±2℃ and a relative humidity of 60%±10% for 12 months. Take samples once at the 0th, 12th, 24th, and 36th months during the test to investigate the long-term stability of the preparation containing the hibiscus flower extract.

[0086] Moisture content: Moisture content was determined according to the fourth method (toluene method) of the moisture determination method in Part IV (General Rule 0832) of the 2015 edition of the Chinese Pharmacopoeia.

[0087] Content: The content of hyperoside in each hibiscus flower was determined according to the method in the literature (Lu Linling et al. Determination of seven flavonoid components in hibiscus flower by one-test-multiple-evaluation method [J]. Journal of Pharmaceutical Analysis, 2013, 33(12): 2082-2087).

[0088] Disintegration time: The disintegration time was determined according to the disintegration time test method in Part IV (General Chapter 0921) of the 2015 edition of the Chinese Pharmacopoeia.

[0089] Aerobic bacteria count: According to the microbial limit test for non-sterile products in Part IV of the 2015 edition of the Chinese Pharmacopoeia (General Rule 1105): the total number of aerobic bacteria is determined by the microbial count method.

[0090] The results are shown in Table 8.

[0091] Table 8 Long-term stability test results of preparations containing hibiscus flower extract

[0092]

[0093] It can be seen from Table 8 that compared with the initial state of the preparation (0 month), the aerobic bacteria count of preparations JN1, JN5 and JN8 began to increase when stored for 2 years, and the aerobic bacteria count increased greatly when stored for 3 years, while the aerobic bacteria count of preparation JN7 of the present invention was still less than 10 when stored for 2-3 years, indicating that the prescription of preparation 7 of the present invention has good long-term stability.

[0094] Example 4 Preparation of Tablets Containing Hibiscus Mallow Flower Extract

[0095] According to the prescription of the pharmaceutical composition Z7 in Table 2 (wherein the hibiscus flower extract is prepared by using Example 1-1), the hibiscus flower extract and calcium hydrogen phosphate are placed in a mixer and mixed for 5 minutes. An appropriate amount of 70% ethanol is added to make a soft material. The particles are sieved with a 20-mesh sieve and dried at 70°C. The particles are sieved with an 18-mesh sieve. A total of 3% sodium carboxymethyl starch and magnesium stearate are added. The mixture is evenly mixed and tableted according to the specification of 0.66 g / tablet. The tablet weight difference and disintegration time are tested.

[0096] Table 9 Tablet weight difference detection

[0097]

[0098] The results showed that the tablet weights differed little when samples were taken at different times, indicating that the prescription process was feasible.

[0099] Table 10 Tablet disintegration time test

[0100] project Tablet pressing start-up Intermediate Stage Ending Phase Disintegration time (min) 28 27 28

[0101] The results showed that the disintegration time of samples taken at different times was in line with the requirements of the Chinese Pharmacopoeia, with small fluctuations, and the prescription process was feasible.

[0102] The above is a further description of the present invention in conjunction with specific embodiments, but these embodiments are merely exemplary and do not constitute any limitation on the scope of the present invention. It should be understood by those skilled in the art that the details and forms of the technical solution of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, but these modifications and replacements all fall within the scope of protection of the present invention.

Claims

1. A pharmaceutical composition containing a Hibiscus tiliaceus flower extract, characterized in that: The invention is composed of hibiscus flower extract, magnesium stearate and calcium hydrogen phosphate, wherein the mass ratio of the hibiscus flower extract, magnesium stearate and calcium hydrogen phosphate is 400:19-22:8-12, preferably 400:19-22:9-11; more preferably 400:19-22:10; and most preferably 400:20:

10.

2. The pharmaceutical composition according to claim 1, characterized in that The hibiscus flower extract is an ethanol extract of hibiscus flower.

3. The pharmaceutical composition according to claim 1, characterized in that The preparation method of the hibiscus flower extract comprises the following steps: adding ethanol to the hibiscus flower and heating and refluxing to extract the hibiscus flower extract.

4. The pharmaceutical composition according to claim 3, characterized in that The volume percentage of the ethanol is 90-98%, preferably 92-98%, and more preferably 92-95%.

5. The pharmaceutical composition according to claim 1, characterized in that The preparation method of the hibiscus flower extract comprises the following steps: (1) adding ethanol to hibiscus flowers, heating under reflux, filtering, and obtaining a filtrate; (2) concentrating the obtained filtrate under reduced pressure to obtain a concentrated solution; (3) Adjust the pH value of the concentrate, refrigerate and let stand, remove the oil layer, dry and grind to obtain the concentrate.

6. The pharmaceutical composition according to claim 5, characterized in that The volume percentage of ethanol in step (1) is 90-98%, preferably 92-98%, more preferably 92-95%, and even more preferably 95%; And / or the amount of ethanol added in step (1) is 15-20 times the mass of the hibiscus flower; preferably 16-20 times, more preferably 17-19 times; further preferably 18 times; And / or the reflux time in step (1) is 0.5-3 hours; preferably 0.5-2.5 hours, more preferably 0.5-2 hours, and even more preferably 1 hour.

7. The pharmaceutical composition according to claim 5, characterized in that The reduced pressure concentration in step (2) is to concentrate to a relative density of 1.10-1.25 at 50° C.; preferably 1.12-1.25; more preferably 1.12-1.23; and even more preferably 1.

20.

8. The pharmaceutical composition according to claim 5, characterized in that The pH value in step (3) is 5.8-7; more preferably 6-7; more preferably 6-6.8; more preferably 6; And / or the refrigerated standing is: standing at -4-4°C for 24-48 hours; preferably standing at 0-4°C for 24-48 hours; more preferably standing at 0-4°C for 24 hours.

9. The method for preparing the pharmaceutical composition according to any one of claims 1 to 8, characterized in that: The steps include: (1) wet-granulating the formulated amount of hibiscus flower extract and calcium hydrogen phosphate to obtain mixed granules; (2) uniformly mixing the mixed granules obtained in step (1) and the formulated amount of magnesium stearate, Preferably, the binder used in the wet granulation is ethanol, more preferably 55-80 v / v% ethanol; more preferably 60-80 v / v% ethanol; more preferably 60-75 v / v% ethanol.

10. A method for improving the stability of hibiscus flower extract, characterized in that: The mass ratio of hibiscus flower extract, magnesium stearate and calcium hydrogen phosphate is adjusted to 400:19-22:8-12, preferably 400:19-22:9-11; more preferably 400:19-22:10; most preferably 400:20:

10.

11. Use of the pharmaceutical composition according to any one of claims 1 to 8 or the method according to claim 10 in the preparation of a hibiscus flower extract preparation.

12. A preparation containing a Hibiscus tiliaceus flower extract, characterized in that: The method is prepared by the pharmaceutical composition according to any one of claims 1 to 8 or the method according to claim 10.

13. The preparation according to claim 12, characterized in that The preparation is capsule, tablet or granule.

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