CN113133976B - A dripping pill containing ginkgolide as effective component - Google Patents
A dripping pill containing ginkgolide as effective component Download PDFInfo
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Abstract
The invention provides a dripping pill with the effective component containing ginkgolide, which also comprises polyethylene glycol and sucrose ester. The effective components of the dripping pill provided by the invention can be quickly dissolved out and enter blood, and the bioavailability of the ginkgolide dripping pill taken by people with stomach power deficiency is expected to be improved. Moreover, the hardness of the dripping pill containing the ginkgolide as the active ingredient can reach 20-25 KN, the roundness can reach 4-5 minutes, the tailing condition can reach 7-9 minutes, and the dripping pill has excellent appearance quality.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a dripping pill containing ginkgolide as an active ingredient.
Background
Cardiovascular and cerebrovascular diseases are diseases which are extremely harmful to human beings, and mainly comprise hypertension, coronary heart disease, stroke and the like. The diseases have the characteristics of high disease probability, high disease disability rate, high disease fatality rate and high recurrence rate. The middle aged and the elderly people over 50 years old are the high-incidence people of the diseases.
The ginkgo leaf extract is a botanical drug which is widely applied internationally and is mainly used for treating and preventing cardiovascular and cerebrovascular diseases and metabolic diseases. The main active ingredients of the ginkgo leaf extract are flavonoid compounds and ginkgo terpene lactone compounds. Among them, ginkgolide has a significant antagonistic action against Platelet Activating Factor (PAF), which is currently considered to be the PAF factor antagonist having the most promising clinical application prospect, and ginkgolide compounds include ginkgolide a, ginkgolide B, ginkgolide C, ginkgolide J, ginkgolide M, ginkgolide K, bilobalide, and the like. Pharmacological research shows that the ginkgolide component also has the effects of resisting oxidation, resisting free radicals, protecting nerves and the like, and has obvious curative effect on cardiovascular and cerebrovascular diseases.
The existing ginkgolide preparation is mainly an injection preparation and a tablet, and in recent years, a ginkgolide dripping pill preparation also appears on the market. The ginkgolide dripping pills have the characteristics of high release speed, high bioavailability and high dissolution rate, but the dissolution rate of the existing ginkgolide dripping pills is mainly examined to find the dissolution rate of the dripping pills in a high rotating speed (100-120 r/min) or a small cup (100-250 ml) dissolution medium, for example, Wuyun and the like disclose that 75% ethanol is used as a solvent in the dissolution rate determination methodology research of the ginkgolide dripping pills, the rotating speed is 100rpm, the operation is carried out according to the small cup method, and the ginkgolide A, B can be completely dissolved after 45min sampling determination; chinese patent CN 107753445A discloses a ginkgolide K drop pill and its preparation method, which discloses that the dissolution rate of the ginkgolide K drop pill can reach more than 80% after 40min under the condition of 120r/min of rotation speed and deionized water as dissolution medium. However, the crowd taking the ginkgolide dripping pills is mainly middle-aged and old people over 50 years old, the middle-aged and old people usually have weak stomach muscle contraction force, low contraction frequency, insufficient stomach power and poor decomposition capability of the medicines, and the dissolution rate detection of the existing dripping pills is carried out in a small cup of dissolution medium (100-250 ml) at the rotating speed of 100-120 r/min, namely the crowd with strong stomach power, so that the basis cannot be provided for the treatment effect of the crowd with the insufficient stomach power.
Therefore, the key point for solving the problem of poor drug absorption capability of middle-aged and old patients is to research and prepare the ginkgolide dripping pill which can still keep high dissolution rate under the condition that the condition is closer to the gastric motility environment condition in the body of the patient taking the ginkgolide dripping pill.
Disclosure of Invention
The invention provides a ginkgolide dripping pill with an active ingredient containing ginkgolide, aiming at solving the technical problem that in the technical field of the prior art, a ginkgolide dripping pill with high dissolution rate still can be maintained under the condition that the condition is closer to the gastric motility environment condition in a patient taking the ginkgolide dripping pill is lacked.
The invention provides a dripping pill with the effective component containing ginkgolide, which also comprises polyethylene glycol and sucrose ester.
The ginkgolide disclosed by the invention can be in the form of a ginkgo leaf extract, and also can be a high-purity monomer compound or a composition thereof.
Further, the polyethylene glycol is selected from one or two of polyethylene glycol 4000 and polyethylene glycol 6000.
Further, the sucrose ester is a compound formed by esterification reaction of sucrose and edible oil or fatty acid; the sucrose ester is selected from one or more of sucrose stearate, sucrose palmitate, sucrose caprylate, sucrose laurate, sucrose myristate, sucrose palmitate and sucrose oleate.
Further, the dripping pill comprises the following components in parts by weight: 5-15 parts of ginkgolide, 20-40 parts of polyethylene glycol and 5-15 parts of sucrose ester.
Furthermore, the dripping pill also comprises 0.5 to 1.5 parts of cellulose.
Further, the cellulose is selected from one or two of microcrystalline cellulose and methyl cellulose.
Further, the hydrophilic-hydrophobic balance value of the sucrose ester is 7-11.
Further, the dripping pill comprises the following components in parts by weight: 8 parts of ginkgolide, 400025 parts of polyethylene glycol, 13 parts of S-770 sucrose ester and 0.5 part of microcrystalline cellulose.
Further, the dripping pill comprises the following components in parts by weight: 12 parts of ginkgolide, 600035 parts of polyethylene glycol, 7 parts of SE 11-sucrose ester and 1.5 parts of methyl cellulose.
The invention also provides a method for preparing the ginkgolide-containing dripping pills as the active ingredients, which comprises the following steps:
s1, sieving the ginkgolide;
s2, heating polyethylene glycol to melt, stirring and adding the ginkgolide prepared in the S1 and other components, and uniformly mixing to obtain a mixture for later use;
and S3, dripping the mixture obtained in the step S2 by using a dripper, and cooling and forming by using condensate.
Advantageous effects
The effective component of the dripping pill containing the ginkgolide as the effective component can be quickly dissolved out. Particularly, when the dripping pill provided by the invention comprises 5-15 parts of ginkgolide, 20-40 parts of polyethylene glycol and 5-15 parts of sucrose ester, even under the conditions of a rotating speed of 75rpm and a dissolving medium of 500ml of hydrochloric acid solution with a pH value of 1.0, the dissolution rate of 15 minutes can still reach 70-80%, and the dissolution rate of 45 minutes can reach more than 95%, so that the bioavailability of the ginkgolide dripping pill taken by people with insufficient gastric motility is expected to be improved, and the dripping pill is particularly suitable for middle-aged and elderly patients.
The dripping pill containing the ginkgolide as the active ingredient has the advantages that the hardness can reach 20-25 KN, the roundness can reach 4-5 minutes, the tailing condition can reach 7-9 minutes, and the dripping pill has excellent appearance quality.
Detailed Description
Unless otherwise indicated, the raw materials and equipment described in the mode of the specific test examples of the present invention are known and commercially available products.
The ginkgolide can be a ginkgo leaf extract, and also can be a monomeric compound with high purity or a composition thereof.
The ginkgolide can be obtained by separation and purification in the prior art, and further can be obtained by a solvent extraction method, a column extraction method, a solvent extraction-column extraction method, a supercritical extraction method, a chromatography or column chromatography purification method and the like.
Preferably, the ginkgolides of the present invention are obtained by the method disclosed in WO 2013159412a 1.
The ginkgolides of the present invention may also be obtained in a commercially available manner.
The hydrophilic-hydrophobic balance of the sucrose ester of the present invention, i.e., HLB of the sucrose ester, in a specific embodiment, the sucrose ester used in the present invention may be SE 15-sucrose ester (HLB15), sucrose palmitate also known as SE 16-sucrose ester (HLB 16), sucrose octanoate also known as SE 8-sucrose ester (HLB 8), sucrose laurate also known as SE 12-sucrose ester (HLB 12), sucrose ester P-1570 (HLB15), sucrose myristate also known as SE 14-sucrose ester (HLB14), sucrose ester S-370 (HLB 3), sucrose ester S-770 (HLB 7), or sucrose ester SE 11-HLB 11; in the specific embodiment, when the HLB of sucrose ester is 7-11 (examples 10 and 11), the highest quality ginkgolide dripping pill can be obtained by compounding sucrose ester with cellulose.
The preparation method of the dripping pill containing the ginkgolide as the active ingredient comprises the following steps of mixing the ginkgo terpene lactone and the water, adding the mixture of the ginkgo terpene lactone and the water into a container, and cooling the container to obtain the dripping pill.
Example 1
Ginkgo terpene lactone 0.5kg (5 parts) polyethylene glycol 40001.5kg (15 parts)
SE 15-sucrose ester 0.5kg (5 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 4000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature.
Example 2
Prescription: ginkgo terpene lactone 1.5kg (15 parts) polyethylene glycol 60004.5kg (45 parts)
P-1570 sucrose ester 1.5kg (15 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 6000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature to obtain the final product.
Example 3
Prescription: ginkgo terpene lactone 0.5kg (5 parts) polyethylene glycol 40002kg (20 parts)
SE 15-sucrose ester 0.5kg (5 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 4000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature.
Example 4
Prescription: ginkgo terpene lactone 1.5kg (15 parts) polyethylene glycol 60004kg (40 parts)
Sucrose palmitate (SE 16-sucrose ester) 1.5kg (15 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 6000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature to obtain the final product.
Example 5
Prescription: ginkgo terpene lactone 0.75kg (7.5 parts) polyethylene glycol 40002.5kg (25 parts)
Polyethylene glycol 60001.5kg (15 parts) sucrose octanoate (SE 8-sucrose ester) 0.75kg (7.5 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 4000 and polyethylene glycol 6000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in 15 deg.C liquid paraffin for molding, wiping off condensate adhered on the surface, and drying at low temperature to obtain the final product.
Example 6
Prescription: ginkgo terpene lactone 1kg (10 parts) polyethylene glycol 40004kg (40 parts)
1kg (10 parts) of sucrose laurate (SE 12-sucrose ester)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 4000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature.
Example 7
Prescription: ginkgo terpene lactone 0.5kg (5 parts) polyethylene glycol 60002.5kg (25 parts)
P-1570 sucrose ester 1.5kg (15 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 6000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature to obtain the final product.
Example 8
Prescription: ginkgo terpene lactone 0.8kg (8 parts) polyethylene glycol 40002.5kg (25 parts)
Sucrose myristate (SE 14-sucrose ester) 1.3kg (13 parts) microcrystalline cellulose 0.05kg (0.5 part)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 4000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature.
Example 9
Prescription: ginkgo terpene lactone 1.2kg (12 parts) polyethylene glycol 60003.5kg (35 parts)
S-370 sucrose ester 0.7kg (7 parts) methyl cellulose 0.15kg (1.5 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 6000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature to obtain the final product.
Example 10
Prescription: ginkgo terpene lactone 0.8kg (8 parts) polyethylene glycol 40002.5kg (25 parts)
S-770 sucrose ester 1.3kg (13 parts) microcrystalline cellulose 0.05kg (0.5 part)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 4000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature.
Example 11
Prescription: ginkgo terpene lactone 1.2kg (12 parts) polyethylene glycol 60003.5kg (35 parts)
SE 11-sucrose ester 0.7kg (7 parts) methyl cellulose 0.15kg (1.5 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 6000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature to obtain the final product.
Comparative example 1
Prescription: ginkgo terpene lactone 0.5kg (5 parts) polyethylene glycol 40002kg (20 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 4000 to melt, stirring, adding ginkgolide, mixing to obtain mixture, dripping the mixture with 2.4mm dripper, cooling in 15 deg.C liquid paraffin, removing condensate adhered on surface, and drying at low temperature.
Comparative example 2
Prescription: ginkgo terpene lactones 0.5kg (5 parts) stearic acid 2kg (20 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating stearic acid to melt, stirring, adding ginkgolide, mixing well to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in 15 deg.C liquid paraffin for molding, wiping off condensate adhered on surface, and drying at low temperature.
Comparative example 3
Prescription: ginkgo terpene lactone 0.5kg (5 parts) polyethylene glycol 60002kg (20 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 6000 to melt, stirring, adding ginkgolide, mixing well to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in 15 deg.C liquid paraffin for molding, wiping off condensate adhered on surface, and drying at low temperature.
Comparative example 4
Prescription: ginkgo terpene lactones 1.5kg (15 parts) P-1570 sucrose palmitate 3kg (30 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating P-1570 sucrose palmitate to melt, stirring, adding ginkgolide, mixing to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in 15 deg.C liquid paraffin, removing condensate adhering to surface, and drying at low temperature.
Comparative example 5
Prescription: ginkgo terpene lactones 1.2kg (12 parts) P-1570 sucrose palmitate 1.5kg (15 parts)
Polyoxyethylene monostearate 1.5kg (15 parts) croscarmellose sodium 0.15kg (1.5 parts)
The preparation process comprises the following steps: sieving ginkgolide with a 60-mesh sieve, heating P-1570 sucrose palmitate and polyoxyethylene monostearate to melt, stirring, adding ginkgolide and other components, mixing well to obtain a mixture, dripping the mixture by 2.4mm drippers, cooling and molding in 15 deg.C liquid paraffin, wiping off condensate adhered to the surface, and drying at low temperature to obtain the final product.
Comparative example 6
Prescription: ginkgo terpene lactone 0.75kg (7.5 parts) polyethylene glycol 40002.5kg (25 parts)
Polyethylene glycol 60001.5kg (15 parts) Tween-800.75 kg (7.5 parts)
CMC-Na 0.45kg (4.5 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 4000 and polyethylene glycol 6000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in 15 deg.C liquid paraffin for molding, wiping off condensate adhered on the surface, and drying at low temperature to obtain the final product.
Comparative example 7
Prescription: ginkgo terpene lactone 1kg (10 parts) polyethylene glycol 60002.5kg (25 parts)
Soya bean lecithin 0.05kg (0.5 parts)
The preparation process comprises the following steps: sieving ginkgolide with 60 mesh sieve, heating polyethylene glycol 6000 to melt, stirring, adding ginkgolide and other components, mixing well to obtain mixture, dripping all the mixture with 2.4mm dripper, cooling in liquid paraffin at 15 deg.C for molding, wiping off condensate adhered on surface, and drying at low temperature to obtain the final product.
The advantageous effects of the present invention are further described below by way of test examples.
Test example 1
Taking examples 1-7 and comparative examples 1-7 of the invention to study the dissolution rates of the ginkgolide dripping pills at 15, 30 and 45 minutes under the conditions of 75rpm of rotation speed and 500ml of hydrochloric acid solution with pH1.0 of dissolution medium, the experimental results are shown in Table 1.
The invention discloses a method for measuring the dissolution rate of a ginkgolide dripping pill, which comprises the following steps: the dissolution rate is examined by adopting a second method, namely a paddle method, of the section 0931 of the general rule of Chinese pharmacopoeia 2015 edition. The dissolution temperature is 37 deg.C, the rotation speed is 75rpm, the dissolution medium is 500ml hydrochloric acid solution with pH1.0, sampling is carried out for 15min, 30min and 45min to detect the content of ginkgolides, and the dissolution rate is calculated.
TABLE 1 dissolution test of ginkgolide dripping pills in hydrochloric acid solution of pH1.0
| Item | Dissolution rate of 15min | Dissolution rate of 30min | Dissolution rate of 45min |
| Comparative example 1 | 42.9％ | 50.4％ | 61.5％ |
| Comparative example 2 | 44.7％ | 56.3％ | 64.5％ |
| Comparative example 3 | 43.5％ | 50.9％ | 61.2％ |
| Comparative example 4 | 32.6％ | 48.6％ | 57.5％ |
| Comparative example 5 | 50.9％ | 74.0％ | 79.9％ |
| Comparative example 6 | 60.8％ | 69.6％ | 78.6％ |
| Comparative example 7 | 58.1％ | 70.9％ | 79.6％ |
| Example 1 | 65.5％ | 74.5％ | 87.6％ |
| Example 2 | 64.7％ | 72.3％ | 84.3％ |
| Example 3 | 70.4％ | 88.7％ | 99.6％ |
| Example 4 | 72.3％ | 86.2％ | 99.1％ |
| Example 5 | 71.9％ | 89.6％ | 99.3％ |
| Example 6 | 73.6％ | 87.1％ | 99.2％ |
| Example 7 | 72.4％ | 88.3％ | 99.8％ |
Experimental example 1 research results show that the ginkgolide dripping pills (examples 1-7) prepared by the invention have excellent dissolution effects in hydrochloric acid solution with pH of 1.0 at the rotation speed of 75rpm and 500ml at 15min, 30min and 45min, and have higher dissolution speed than other ginkgolide dripping pills (comparative examples 1-7).
The inventor researches the dissolution rate of the ginkgolide dripping pill in 500ml of hydrochloric acid solution with pH1.0 at the rotating speed of 75rpm by singly compounding one substrate and the ginkgolide through a comparative example 1-4, and finds that the ginkgolide dripping pill which reaches the qualified dissolution rate (45min, the dissolution rate is more than 75%) in 500ml of hydrochloric acid solution with pH1.0 at the rotating speed of 75rpm cannot be prepared no matter the substrate is polyethylene glycol 4000, polyethylene glycol 6000, stearic acid or sucrose ester.
The inventors further studied the dissolution effect of ginkgolide drop pills compounded by drug, matrix, surfactant, solubilizer or disintegrant (comparative examples 5-7, examples 1-2), and found that when ginkgolide, polyethylene glycol and sucrose ester are compounded, can prepare ginkgolide dripping pills with superior dissolution in 500ml hydrochloric acid solution with pH1.0 at 75rpm (example 1-2), so that the inventor further studies the mixture ratio of ginkgolide, polyethylene glycol and sucrose ester (example 3-7), and finally finds that when the ginkgolide is 5-15 parts by weight, the polyethylene glycol is 20-40 parts by weight and the sucrose ester is 5-15 parts by weight, the ginkgolide dripping pill can achieve the effect that the drug dissolution rate is more than 95% in 500ml hydrochloric acid solution with the pH value of 1.0 at the rotating speed of 75rpm for 45 min.
The inventor can obtain the ginkgolide dropping pill with the dissolution higher than that of other proportions by only adjusting the proportions of the ginkgolide, the polyethylene glycol and the sucrose ester, which is beyond the expectation of the inventor.
Test example 2
Referring to the requirements of the pill preparation items in Chinese pharmacopoeia 2015 year edition, the ginkgolide pills of examples 1-11 of the invention are checked, the check items are respectively hardness (KN), pill roundness, pill tailing condition (scoring from 0 to 10, 10 being optimal and 0 being worst), dissolution time limit (min), 15min in vitro dissolution rate, 45min in vitro dissolution rate (X > 75%) and the experimental results are shown in Table 2.
The invention discloses a method for measuring the dissolution rate of a ginkgolide dripping pill, which comprises the following steps: the dissolution rate is examined by adopting a second method, namely a paddle method, of the section 0931 of the general rule of Chinese pharmacopoeia 2015 edition. The dissolution temperature is 37 ℃, the rotation speed is 75rpm, 500ml of hydrochloric acid solution with the pH value of 1.0 is dissolved in dissolution medium, samples are taken for 15min and 45min to detect the content of the total ginkgolides, and the dissolution rate is calculated.
The method for measuring the roundness of the dripping pill comprises the following steps: expressed by the shortest diameter/longest diameter of the dripping pill, the ratio is more than 0.95 and is 5 minutes, between 0.9 and 0.95 and is 4 minutes, between 0.85 and 0.9 and is 3 minutes, between 0.8 and 0.85 and is 2 minutes, and below 0.8 and is 1 minute.
TABLE 2 evaluation results of quality of dropping pills
Test example 2 the quality of ginkgolide dropping pills prepared in examples 1 to 11 of the present invention was evaluated. The ginkgolide dripping pills prepared by the invention have excellent hardness, roundness, tailing condition and dissolution.
The inventor finds that the dripping pills prepared by compounding ginkgolide, sucrose ester and polyethylene glycol can quickly dissolve out the active ingredients in the quality evaluation tests of examples 1-7, but the hardness, roundness and tailing conditions of the dripping pills are not optimal. Therefore, the inventors studied the effect of adding cellulose on the hardness, roundness and tailing of ginkgolide drop pills through examples 8-11, and the results showed that the addition of cellulose can significantly improve the hardness, roundness and tailing of ginkgolide drop pills prepared by the present invention. Furthermore, the inventors have surprisingly found that the addition of cellulose improves the hardness, roundness and tailing of the ginkgolide drop pills, and also improves the dissolution rate of the ginkgolide drop pills, especially when the HLB value of sucrose ester in the ginkgolide drop pills is 7-11, the dissolution rate of the ginkgolide drop pills (example 10 and example 11) can reach more than 75% in 15min, which is higher than that of sucrose ester with other HLB values, and the hardness of the drop pills can reach 24-25 KN, the roundness is 5 minutes, and the tailing is 8-9 minutes, which is more than the expectation of the inventors.
Test example 3
The ginkgolide dropping pills prepared in the embodiments 3, 5, 7, 11 and 5 are taken, the pills are fed to rabbits by stomach irrigation according to the dose of 500mg/kg, blood samples are collected for analysis 5min, 10min, 15min, 20min, 30min, 45min, 60min, 2h, 4h and 8h after the pills are taken by the rabbits respectively, the blood concentration of the rabbits (based on the content of the ginkgolide) is determined, and the peak reaching concentration and the peak reaching time of the ginkgolide dropping pills in the rabbits are counted in a table 3.
TABLE 3 Peak-reaching concentration and time of ginkgolide dripping pill in rabbit body
Peak concentration and time to peak refer to the highest concentration value and time of appearance of the drug in plasma after extravascular administration and represent the degree and rate of drug absorption, respectively.
As can be seen from Table 3, the ginkgolide dripping pills prepared by the invention can reach the highest blood concentration more quickly, have higher blood concentration and have earlier peak reaching time in a blood concentration test of rabbits than the comparative example 5. Therefore, the ginkgolide dripping pill disclosed by the invention can exert the drug effect more quickly.
In conclusion, the invention provides a ginkgolide dripping pill preparation and a preparation method thereof, the preparation can be quickly dissolved out in 500ml of hydrochloric acid solution with pH value of 1.0 at the rotating speed of 75rpm and a dissolving medium and can enter blood, and the preparation is expected to achieve a treatment effect more quickly when being taken by people with insufficient gastric motility.
The above description is only a preferred embodiment of the present invention, and it should be understood that the present invention is not limited to the above description, which should be interpreted as a limitation, since modifications can be made to the embodiment and its application range by those skilled in the art in light of the above description.
Claims (10)
1. A dripping pill containing ginkgolide as effective component is characterized by further comprising polyethylene glycol and sucrose ester.
2. The dripping pill according to claim 1, wherein the polyethylene glycol is selected from one or two of polyethylene glycol 4000 and polyethylene glycol 6000.
3. The dropping pill according to claim 2, wherein the sucrose ester is a compound formed by esterification of sucrose with an edible oil or fat or a fatty acid; the sucrose ester is selected from one or more of sucrose stearate, sucrose palmitate, sucrose caprylate, sucrose laurate, sucrose myristate, sucrose palmitate and sucrose oleate.
4. The dripping pill according to any one of claims 1 to 3, wherein the dripping pill comprises the following components in parts by weight: 5-15 parts of ginkgolide, 20-40 parts of polyethylene glycol and 5-15 parts of sucrose ester.
5. The dripping pill according to claim 4, wherein the dripping pill further comprises 0.5-1.5 parts of cellulose.
6. The dripping pill according to claim 5, wherein the cellulose is selected from one or both of microcrystalline cellulose and methylcellulose.
7. The dropping pill according to claim 6, wherein the sucrose ester has a hydrophilic-hydrophobic equilibrium value of 7 to 11.
8. The dripping pill according to claim 7, wherein the dripping pill comprises the following components in parts by weight: 8 parts of ginkgolide, 400025 parts of polyethylene glycol, 13 parts of S-770 sucrose ester and 0.5 part of microcrystalline cellulose.
9. The dripping pill according to claim 7, wherein the dripping pill comprises the following components in parts by weight: 12 parts of ginkgolide, 600035 parts of polyethylene glycol, 7 parts of SE 11-sucrose ester and 1.5 parts of methyl cellulose.
10. Method for the preparation of the dripping pill according to any of claims 1 to 9, comprising the steps of:
s1, sieving the ginkgolide;
s2, heating polyethylene glycol to melt, stirring and adding the ginkgolide prepared in the S1 and other components, and uniformly mixing to obtain a mixture for later use;
and S3, dripping the mixture obtained in the step S2 by using a dripper, and cooling and forming by using condensate.
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