A pharmaceutical composition and a method for preparing the same

Abstract

The application discloses a kind of pharmaceutical composition and preparation method thereof.It is made of the following weight parts raw material components: quercetin 2-5 parts, kaempferol 1-3 parts, isorhamnetin 3-8 parts, isoginkgetin 3-8 parts, ginsenoside Rg1 1-3 parts, ginsenoside Rb1 3-8 parts, ginsenoside Rf 3-8 parts, starch 15-50 parts, calcium carbonate 10-30 parts, water 30-120 parts.The pharmaceutical composition of the application directly uses the main active components in ginseng extract and ginkgo biloba leaf extract.It is found through experimental research that the combination of isorhamnetin and isoginkgetin in the component, the combination of ginsenoside Rb1 and ginsenoside Rf has synergistic effect.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a pharmaceutical composition and its preparation method. Background Technology

[0002] Xueluotong Capsules are composed of two traditional Chinese medicines: Ginkgo biloba extract and ginseng. They have the effects of invigorating qi, promoting blood circulation, and clearing the meridians. They are used for symptoms such as headache, dizziness, forgetfulness, numbness of limbs, fatigue, and dark purple tongue caused by qi deficiency and blood stasis in the early stage of mild cerebral arteriosclerosis.

[0003] Arteriosclerosis is a non-inflammatory disease of the arteries that causes thickening and hardening of the arterial walls, loss of elasticity, and narrowing of the lumen. It is a vascular disease that develops with age, typically beginning in adolescence and worsening in middle and old age. It is more common in men than women, and its incidence has been gradually increasing in my country in recent years, becoming one of the leading causes of death among the elderly. The manifestations of arteriosclerosis depend primarily on the degree of ischemia in the affected blood vessels and organs. In the early stages of arteriosclerosis, most patients have almost no clinical symptoms. In the middle stages, most patients experience varying degrees of symptoms such as palpitations, chest pain, chest tightness, headache, dizziness, cold and numb extremities, weakness and fatigue in the limbs, claudication, decreased vision, memory loss, insomnia, and vivid dreams.

[0004] While Xueluotong capsules have some therapeutic effect on mild arteriosclerosis, the effect is not significant and cannot treat patients with moderate or severe arteriosclerosis. This is because the active ingredients in ginkgo leaf extract and ginseng extract are complex, making it difficult to identify the main active components and control the antagonistic interactions between them. According to research, the main active components in ginkgo leaf extract of Xueluotong capsules are quercetin, kaempferol, and isorhamnetin, while the main active components in ginseng extract are ginsenoside Rg1, ginsenoside Re, and ginsenoside Rb1. However, even when these components are combined in a moderate weight ratio, the effect is unsatisfactory, suggesting that there are more important undiscovered components in Xueluotong capsules. Summary of the Invention

[0005] The purpose of this invention is to provide a pharmaceutical composition and a method for preparing the same.

[0006] A pharmaceutical composition comprising the following raw material components in parts by weight: quercetin 2-5 parts, kaempferol 1-3 parts, isorhamnetin 3-8 parts, isoginkgolide 3-8 parts, ginsenoside Rg1 1-3 parts, ginsenoside Rb1 3-8 parts, ginsenoside Rf 3-8 parts, starch 15-50 parts, calcium carbonate 10-30 parts, and water 30-120 parts.

[0007] The preparation method of the pharmaceutical composition is carried out according to the following steps:

[0008] (1) Take 15-50 parts of starch and 10-30 parts of calcium carbonate by weight and mix them in a wet granulation machine at low speed for 3-8 minutes.

[0009] (2) Add 2-5 parts of quercetin, 1-3 parts of kaempferol, 3-8 parts of isorhamnetin, 3-8 parts of isoginkgoside, 1-3 parts of ginsenoside Rg1, 3-8 parts of ginsenoside Rb1, and 3-8 parts of ginsenoside Rf; stir at high speed for 3-8 minutes; then add water while stirring at high speed for 5-10 minutes, the amount of water added is 30-120 parts; to obtain a soft material;

[0010] (3) Place the soft material prepared in step (2) into a swing pellet mill and pass it through a 12-28 mesh steel sieve to make wet pellets. Then transfer the wet pellets to a drying tray for drying.

[0011] (4) Place the dried granules prepared in step (3) into a swing granulator and pass them through a 20-40 mesh steel sieve for granulation. Weigh the dry granules after mixing and fill them into hollow capsules to make inner capsules for later use.

[0012] The conditions for low-speed mixing in step (1) are: stirring speed of 30-60 rpm, and the side blade speed of 300-600 rpm.

[0013] The conditions for low-speed mixing in step (2) are: stirring speed of 30-60 rpm, and the side blade speed of 300-600 rpm; the conditions for high-speed mixing are: stirring speed of 90-180 rpm, and the side blade speed of 900-1800 rpm.

[0014] The drying temperature in step (3) is 50-60℃.

[0015] The total mixing is carried out by placing the granulated particles in an EYH-2000 two-dimensional motion mixer and operating it according to the equipment's SOP.

[0016] The amount weighed in step (4) is 0.1-0.3g / particle.

[0017] The beneficial effects of this invention: The pharmaceutical composition of this invention directly utilizes the main active components from ginseng extract and ginkgo leaf extract. Experimental studies have revealed that the combination of isorhamnetin and isoginkgolide, and the combination of ginsenoside Rb1 and ginsenoside Rf, exhibit synergistic effects. Detailed Implementation

[0018] To facilitate understanding of the present invention, a more comprehensive description will be given below. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of the present invention.

[0019] Example 1

[0020] A pharmaceutical composition is made from the following raw material components in parts by weight: quercetin 4 parts, kaempferol 2 parts, isorhamnetin 6 parts, isoginkgolide 6 parts, ginsenoside Rg1 2 parts, ginsenoside Rb1 6 parts, ginsenoside Rf 6 parts, starch 30 parts, calcium carbonate 20 parts, and water 80 parts.

[0021] The preparation method of the pharmaceutical composition is carried out according to the following steps:

[0022] (1) Take 30 parts starch and 20 parts calcium carbonate by weight and mix them at low speed for 6 minutes in a wet mixing granulator. The conditions for low-speed mixing are: stirring speed of 40 rpm and side blade speed of 400 rpm.

[0023] (2) Add 4 parts quercetin, 2 parts kaempferol, 6 parts isorhamnetin, 6 parts isoginkgoside, 2 parts ginsenoside Rg1, 6 parts ginsenoside Rb1, and 6 parts ginsenoside Rf; stir at high speed for 6 minutes; then add water while stirring at high speed for 8 minutes, with the amount of water added being 80 parts; to obtain a soft material; the conditions for low-speed mixing are: stirring speed of 50 rpm, while adjusting the side blade speed to 400 rpm; the conditions for high-speed mixing are: stirring speed of 130 rpm, while adjusting the side blade speed to 1200 rpm;

[0024] (3) Place the soft material prepared in step (2) into a swing pellet mill and pass it through a 16-mesh steel sieve to make wet pellets. Then transfer the wet pellets to a drying tray for drying. The drying temperature is 55℃.

[0025] (4) Place the dried granules prepared in step (3) into a swing granulator and pass them through a 30-mesh steel sieve for granulation. Weigh the dry granules after total mixing, adjust the filling amount to 0.18g / granule, and fill them into hollow capsules to make inner capsules for later use. The total mixing is carried out by placing the granulated granules in an EYH-2000 two-dimensional motion mixer and operating it according to the SOP of the equipment.

[0026] Example 2

[0027] A pharmaceutical composition is made from the following raw material components in parts by weight: quercetin 2 parts, kaempferol 1 part, isorhamnetin 4 parts, isoginkgolide 4 parts, ginsenoside Rg1 1 part, ginsenoside Rb1 4 parts, ginsenoside Rf 4 parts, starch 16 parts, calcium carbonate 10 parts, and water 40 parts.

[0028] The preparation method of the pharmaceutical composition is carried out according to the following steps:

[0029] (1) Take 16 parts starch and 10 parts calcium carbonate by weight and mix them at low speed for 4 minutes in a wet mixing granulator. The conditions for low-speed mixing are: stirring speed of 35 rpm and side blade speed of 350 rpm.

[0030] (2) Add 2 parts quercetin, 1 part kaempferol, 4 parts isorhamnetin, 4 parts isoginkgoside, 1 part ginsenoside Rg1, 4 parts ginsenoside Rb1, and 4 parts ginsenoside Rf; stir at high speed for 4 minutes; then add water while stirring at high speed for 6 minutes, with the amount of water added being 40 parts; to obtain a soft material; the conditions for low-speed mixing are: stirring speed of 35 rpm, while adjusting the side blade speed to 300 rpm; the conditions for high-speed mixing are: stirring speed of 90 rpm, while adjusting the side blade speed to 900 rpm;

[0031] (3) Place the soft material prepared in step (2) into a swing pellet mill and pass it through a 12-mesh steel sieve to make wet pellets. Then transfer the wet pellets to a drying tray for drying. The drying temperature is 50℃.

[0032] (4) Place the dried granules prepared in step (3) into a swing granulator and pass them through a 20-mesh steel sieve for granulation. Weigh the dry granules after total mixing, adjust the filling amount to 0.18g / granule, and fill them into hollow capsules to make inner capsules for later use. The total mixing is carried out by placing the granulated granules in an EYH-2000 two-dimensional motion mixer and operating it according to the SOP of the equipment.

[0033] Example 3

[0034] A pharmaceutical composition is made from the following raw material components in parts by weight: 5 parts quercetin, 3 parts kaempferol, 8 parts isorhamnetin, 8 parts isoginkgoside, 3 parts ginsenoside Rg1, 8 parts ginsenoside Rb1, 8 parts ginsenoside Rf, 50 parts starch, 30 parts calcium carbonate, and 120 parts water.

[0035] The preparation method of the pharmaceutical composition is carried out according to the following steps:

[0036] (1) Take 50 parts of starch and 30 parts of calcium carbonate by weight and mix them at low speed for 8 minutes in a wet mixing granulator. The conditions for low-speed mixing are: stirring speed of 60 rpm and side blade speed of 600 rpm.

[0037] (2) Add 5 parts quercetin, 3 parts kaempferol, 8 parts isorhamnetin, 8 parts isoginkgoside, 3 parts ginsenoside Rg1, 8 parts ginsenoside Rb1, and 8 parts ginsenoside Rf; stir at high speed for 8 minutes; then add water while stirring at high speed for 10 minutes, with the amount of water added being 120 parts; to obtain a soft material; the conditions for low-speed mixing are: stirring speed of 60 rpm, while adjusting the side blade speed to 600 rpm; the conditions for high-speed mixing are: stirring speed of 180 rpm, while adjusting the side blade speed to 1800 rpm;

[0038] (3) Place the soft material prepared in step (2) into a swing pellet mill and pass it through a 28-mesh steel sieve to make wet pellets. Then transfer the wet pellets to a drying tray for drying. The drying temperature is 60℃.

[0039] (4) Place the dried granules prepared in step (3) into a swing granulator and pass them through a 40-mesh steel sieve for granulation. Weigh the dry granules after total mixing, adjust the filling amount to 0.18g / granule, and fill them into hollow capsules to make inner capsules for later use. The total mixing is carried out by placing the granulated granules in an EYH-2000 two-dimensional motion mixer and operating it according to the SOP of the equipment.

[0040] Comparative Example 1

[0041] A pharmaceutical composition is made from the following raw material components in parts by weight: quercetin 4 parts, kaempferol 2 parts, isorhamnetin 12 parts, ginsenoside Rg1 2 parts, ginsenoside Rb1 6 parts, ginsenoside Rf 6 parts, starch 30 parts, calcium carbonate 20 parts, and water 80 parts.

[0042] The preparation method of the pharmaceutical composition is carried out according to the following steps:

[0043] (1) Take 30 parts starch and 20 parts calcium carbonate by weight and mix them at low speed for 6 minutes in a wet mixing granulator. The conditions for low-speed mixing are: stirring speed of 40 rpm and side blade speed of 400 rpm.

[0044] (2) Add 4 parts quercetin, 2 parts kaempferol, 12 parts isorhamnetin, 2 parts ginsenoside Rg1, 6 parts ginsenoside Rb1, and 6 parts ginsenoside Rf; stir at high speed for 6 minutes; then add water while stirring at high speed for 8 minutes, with the amount of water added being 80 parts; to obtain a soft material; the conditions for low-speed mixing are: stirring speed of 50 rpm, while adjusting the side blade speed to 400 rpm; the conditions for high-speed mixing are: stirring speed of 130 rpm, while adjusting the side blade speed to 1200 rpm;

[0045] (3) Place the soft material prepared in step (2) into a swing pellet mill and pass it through a 16-mesh steel sieve to make wet pellets. Then transfer the wet pellets to a drying tray for drying. The drying temperature is 55℃.

[0046] (4) Place the dried granules prepared in step (3) into a swing granulator and pass them through a 30-mesh steel sieve for granulation. Weigh the dry granules after total mixing, adjust the filling amount to 0.18g / granule, and fill them into hollow capsules to make inner capsules for later use. The total mixing is carried out by placing the granulated granules in an EYH-2000 two-dimensional motion mixer and operating it according to the SOP of the equipment.

[0047] Comparative Example 2

[0048] A pharmaceutical composition is made from the following raw material components in parts by weight: quercetin 4 parts, kaempferol 2 parts, isoginkgolide 12 parts, ginsenoside Rg1 2 parts, ginsenoside Rb1 6 parts, ginsenoside Rf 6 parts, starch 30 parts, calcium carbonate 20 parts, and water 80 parts.

[0049] The preparation method of the pharmaceutical composition is carried out according to the following steps:

[0050] (1) Take 30 parts starch and 20 parts calcium carbonate by weight and mix them at low speed for 6 minutes in a wet mixing granulator. The conditions for low-speed mixing are: stirring speed of 40 rpm and side blade speed of 400 rpm.

[0051] (2) Add 4 parts quercetin, 2 parts kaempferol, 12 parts isoginkgolide, 2 parts ginsenoside Rg1, 6 parts ginsenoside Rb1, and 6 parts ginsenoside Rf; stir at high speed for 6 minutes; then add water while stirring at high speed for 8 minutes, with the amount of water added being 80 parts; to obtain a soft material; the conditions for low-speed mixing are: stirring speed of 50 rpm, while adjusting the side blade speed to 400 rpm; the conditions for high-speed mixing are: stirring speed of 130 rpm, while adjusting the side blade speed to 1200 rpm;

[0052] (3) Place the soft material prepared in step (2) into a swing pellet mill and pass it through a 16-mesh steel sieve to make wet pellets. Then transfer the wet pellets to a drying tray for drying. The drying temperature is 55℃.

[0053] (4) Place the dried granules prepared in step (3) into a swing granulator and pass them through a 30-mesh steel sieve for granulation. Weigh the dry granules after total mixing, adjust the filling amount to 0.18g / granule, and fill them into hollow capsules to make inner capsules for later use. The total mixing is carried out by placing the granulated granules in an EYH-2000 two-dimensional motion mixer and operating it according to the SOP of the equipment.

[0054] Comparative Example 3

[0055] A pharmaceutical composition is made from the following raw material components in parts by weight: quercetin 4 parts, kaempferol 2 parts, isorhamnetin 6 parts, isoginkgolide 6 parts, ginsenoside Rg1 2 parts, ginsenoside Rb1 12 parts, starch 30 parts, calcium carbonate 20 parts, and water 80 parts.

[0056] The preparation method of the pharmaceutical composition is carried out according to the following steps:

[0057] (1) Take 30 parts starch and 20 parts calcium carbonate by weight and mix them at low speed for 6 minutes in a wet mixing granulator. The conditions for low-speed mixing are: stirring speed of 40 rpm and side blade speed of 400 rpm.

[0058] (2) Add 4 parts quercetin, 2 parts kaempferol, 6 parts isorhamnetin, 6 parts isoginkgoside, 2 parts ginsenoside Rg1, and 12 parts ginsenoside Rb1; stir at high speed for 6 minutes; then add water while stirring at high speed for 8 minutes, with the amount of water added being 80 parts; to obtain a soft material; the conditions for low-speed mixing are: stirring speed of 50 rpm, while adjusting the side blade speed to 400 rpm; the conditions for high-speed mixing are: stirring speed of 130 rpm, while adjusting the side blade speed to 1200 rpm;

[0059] (3) Place the soft material prepared in step (2) into a swing pellet mill and pass it through a 16-mesh steel sieve to make wet pellets. Then transfer the wet pellets to a drying tray for drying. The drying temperature is 55℃.

[0060] (4) Place the dried granules prepared in step (3) into a swing granulator and pass them through a 30-mesh steel sieve for granulation. Weigh the dry granules after total mixing, adjust the filling amount to 0.18g / granule, and fill them into hollow capsules to make inner capsules for later use. The total mixing is carried out by placing the granulated granules in an EYH-2000 two-dimensional motion mixer and operating it according to the SOP of the equipment.

[0061] Comparative Example 4

[0062] A pharmaceutical composition is made from the following raw material components in parts by weight: quercetin 4 parts, kaempferol 2 parts, isorhamnetin 6 parts, isoginkgolide 6 parts, ginsenoside Rg1 2 parts, ginsenoside Rf 12 parts, starch 30 parts, calcium carbonate 20 parts, and water 80 parts.

[0063] The preparation method of the pharmaceutical composition is carried out according to the following steps:

[0064] (1) Take 30 parts starch and 20 parts calcium carbonate by weight and mix them at low speed for 6 minutes in a wet mixing granulator. The conditions for low-speed mixing are: stirring speed of 40 rpm and side blade speed of 400 rpm.

[0065] (2) Add 4 parts quercetin, 2 parts kaempferol, 6 parts isorhamnetin, 6 parts isoginkgoside, 2 parts ginsenoside Rg1, and 12 parts ginsenoside Rf; stir at high speed for 6 minutes; then add water while stirring at high speed for 8 minutes, the amount of water added is 80 parts; to obtain a soft material; the conditions for low-speed mixing are: stirring speed of 50 rpm, while adjusting the side blade speed to 400 rpm; the conditions for high-speed mixing are: stirring speed of 130 rpm, while adjusting the side blade speed to 1200 rpm;

[0066] (3) Place the soft material prepared in step (2) into a swing pellet mill and pass it through a 16-mesh steel sieve to make wet pellets. Then transfer the wet pellets to a drying tray for drying. The drying temperature is 55℃.

[0067] (4) Place the dried granules prepared in step (3) into a swing granulator and pass them through a 30-mesh steel sieve for granulation. Weigh the dry granules after total mixing, adjust the filling amount to 0.18g / granule, and fill them into hollow capsules to make inner capsules for later use. The total mixing is carried out by placing the granulated granules in an EYH-2000 two-dimensional motion mixer and operating it according to the SOP of the equipment.

[0068] Experimental Example 1:

[0069] Sixty Kunming mice, weighing 18-22g, were randomly divided into 6 groups of 10 mice each. The control group was administered the same volume of distilled water by gavage; the drug compositions prepared in Examples 1-3 and Comparative Examples 1-2 were administered by gavage at a dose of 1.2g crude drug / kg. The drugs were administered once daily for 7 consecutive days. Two hours after the last administration, the mice were intraperitoneally injected with 0.1ml / 10g of 0.45% sodium pentobarbital. The mice were then fixed prone on an observation table, and paraffin oil was dripped onto the outer ear. The microcirculation of the normal mouse ear was observed using a 6×10 microscope. At this time, 0.1μg of epinephrine hydrochloride was injected subcutaneously to induce microcirculatory disturbance. The recovery of microcirculation was observed, and the time required for the restoration of normal microvascular flow was recorded (Table 1).

[0070] Table 1 Effects on mouse auricular microcirculation

[0071]

[0072]

[0073] Note: * indicates that compared with Example 1 group, P<0.05.

[0074] Experimental Example 2:

[0075] Sixty Kunming mice, weighing 18-22g, were randomly divided into 6 groups of 10 mice each. The control group was administered the same volume of distilled water by gavage; the drug compositions prepared in Examples 1-3 and Comparative Examples 3-4 were administered at a dose of 1.2g crude drug / kg by gavage. The mice were administered the drugs once daily for 7 consecutive days. 0.5 hours after the last administration, a 2g lead skewer was placed under the tail of each mouse. The mice were then placed in a 55cm×35cm×30cm glass tank for swimming. The water temperature was 25℃ and the room temperature was 27℃. The swimming time under tail load was observed. Exhaustion was defined as the mouse's nose sinking into the water for 10 seconds and not resurfacing; this was recorded as the immediate swimming time (Table 2).

[0076] Table 2 Effects on anti-fatigue effects in mice

[0077]

[0078] Note: * indicates that compared with Example 1 group, P<0.05.

[0079] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A pharmaceutical composition, characterized by, Quercetin 2-5 parts, kaempferol 1-3 parts, isorhamnetin 3-8 parts, isoginkgetin 3-8 parts, ginsenoside Rg1 1-3 parts, ginsenoside Rb1 3-8 parts, ginsenoside Rf 3-8 parts, starch 15-50 parts, calcium carbonate 10-30 parts, water 30-120 parts.

2. A process for the preparation of a pharmaceutical composition as claimed in claim 1, characterized in that, The following steps are taken: (1) Starch 15-50 parts, calcium carbonate 10-30 parts are taken by weight parts and mixed in a wet granulator at low speed for 3-8 min; (2) Quercetin 2-5 parts, kaempferol 1-3 parts, isorhamnetin 3-8 parts, isoginkgetin 3-8 parts, ginsenoside Rg1 1-3 parts, ginsenoside Rb1 3-8 parts, ginsenoside Rf 3-8 parts are added; high-speed stirring for 3-8 min; then high-speed stirring while adding water for 5-10 min, the amount of water added is 30-120 parts; soft material is obtained; (3) The soft material prepared in step (2) is placed in a swinging granulator to pass through a 12-28 mesh steel sieve to prepare wet granules, and then the wet granules are transferred to a drying tray for drying; (4) The dried granules prepared in step (3) are placed in a swinging granulator to pass through a 20-40 mesh steel sieve to granulate, the total mixed dry granules are weighed, filled into a hollow capsule to prepare an inner capsule for standby.

3. The method of preparing the pharmaceutical composition according to claim 2, wherein, The low-speed mixing condition in step (1) is that the stirring speed is 30-60 rpm, and the side knife speed is adjusted to 300-600 rpm.

4. The method of claim 2, wherein the pharmaceutical composition is prepared by, The high-speed stirring condition in step (2) is that the stirring speed is 90-180 rpm, and the side knife speed is adjusted to 900-1800 rpm.

5. The method of preparing the pharmaceutical composition according to claim 2, wherein, The drying temperature in step (3) is 50-60°C.

6. The method of preparing the pharmaceutical composition according to claim 2, wherein, The total mixing is to place the granulated particles in an EYH-2000 two-dimensional motion mixer and perform total mixing according to the SOP operation of the equipment.

7. The method of preparing the pharmaceutical composition according to claim 2, wherein, The weighing amount in step (4) is 0.1-0.3 g / particle.

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