CN112494444B - Hydrophilic gel sustained release tablet containing echinacoside and preparation method and application thereof - Google Patents
Hydrophilic gel sustained release tablet containing echinacoside and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a hydrophilic gel sustained release tablet containing echinacoside, which comprises the following components: 200-400 parts by weight of echinacoside; 200-400 parts by weight of solubilizing chelating agent; 300-600 parts by weight of release retarder; 100-180 parts of filler; 10-80 parts of glidant; 10-80 parts by weight of coating material; the solubilising chelating agent is selected from one or more of cyclodextrin and derivatives thereof. In vitro experiments show that the sustained release preparation is sustained and released stably within 24 hours, and provides a new choice for preventing and treating diseases such as senile dementia and the like. Compared with the common tablet, the administration times and the dosage are reduced; the compliance of the drug administration of the patients with related diseases is enhanced; the water solubility of the medicine is improved, and the bioavailability of the medicine is improved; improves the medication safety and enhances the curative effect of the echinacoside on senile dementia and other diseases. Meanwhile, the sustained release tablet disclosed by the invention is simple in preparation process and is beneficial to industrial mass production.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a hydrophilic gel sustained-release tablet containing echinacoside, and a preparation method and application thereof.
Background
Sustained release formulations (Sustained release-release preparation) are formulations which delay the release rate of the drug and the delivery rate of the formulation during in vivo release, absorption, distribution, metabolism and excretion by means of the formulation, such as coating, adding a retarder, etc., according to the diffusion, dissolution, permeation and ion exchange of the drug and the gastrointestinal characteristics, thereby achieving a long-acting effect of the drug. In a regulated release medium, the medicine is released slowly and at a constant speed according to the requirement; compared with the corresponding common preparation, the internal blood concentration process is stable, the peak-valley fluctuation percentage is small, and the administration times can be reduced from 3 to 4 times to 1 to 2 times every 24 hours. The oral sustained release preparation is classified into gastric-soluble type and enteric-soluble type according to the release site.
Echinacoside (ECH) is also called Echinacoside and echinacoside, and is derived from rhizome of Echinacea plant, mainly from herba cistanches, and is a phenethyl alcohol glycoside compound. The cistanche deserticola has extremely high medicinal value, and has the effects of tonifying kidney yang, replenishing essence and blood, relaxing bowel and the like. Modern researches have shown that echinacoside can reverse and protect rotenone, middle artery occlusion and 6-hydroxydopamine induced dopaminergic neuron injury. Echinacoside can also pass through blood brain barrier, and can be used for treating neurodegenerative diseases such as Parkinson disease and Alzheimer disease, and preventing and treating cerebral ischemia. Echinacoside can exert obvious neuroprotective effect by reversing mitochondrial function and apoptosis, resisting TNF-alpha (tumor necrosis factor alpha) -induced apoptosis of human neuroblastoma cells, promoting cholinergic neurotransmitter level in vascular dementia mouse brain and other ways, and can be used for intervention of neurodegenerative diseases. Echinacoside also has estrogen-like effect and can be used for treating postmenopausal osteoporosis induced by estrogen deficiency. Echinacoside can protect acute lung injury, and can be used for treating acute respiratory distress syndrome, and also can protect acute mouse liver injury caused by carbon tetrachloride. And echinacoside also has effects of resisting injury, resisting oxidation, relieving inflammation, caring skin, and resisting aging. The pharmacological and metabolic effects of the echinacoside are continuously explored, and the original researches on the effects of anti-injury, anti-infection, anti-oxidation, neuroprotection and the like are carried out until the effects of prolonging the service life, immunoregulation, anti-tumor, anti-fibrosis and the like of the echinacoside are all proved that the echinacoside is a Chinese medicinal extract with great potential.
Modern medical research finds that one of the most main active ingredients of cistanche deserticola is echinacoside. The traditional Chinese medicine of the past records the effects of tonifying kidney and nourishing marrow, replenishing the brain, nourishing the color, reducing weight after long-term administration, prolonging life and the like of cistanche deserticola, and comprises the effects of improving intelligence, enhancing memory, preventing senile dementia and the like. The traditional Chinese medicine preparation has better curative effects on amnesia, senile dementia and the like by using single cistanche medicine or compound containing cistanche as a main ingredient, such as eight immortal pills (Jiu in Yankee Jia Tibetan) and Qixiang tablets (thirteenth book of Chinese medicine preparation in medical standard of Ministry of health of the people's republic of China). Pharmacological activity researches show that the echinacoside has the effects of protecting nerve cells, improving learning and memory capacity, resisting senile dementia, improving brain circulation and the like. Although echinacoside is a known substance with pharmaceutical activity, the dose per day is large, the number of times of administration is large, the safety is low, and the administration is easy to miss.
Disclosure of Invention
In view of the above, the technical problem to be solved by the invention is to provide a hydrophilic gel sustained-release tablet containing echinacoside, and a preparation method and application thereof, so as to achieve the sustained-release effect of the echinacoside.
In order to achieve the above purpose, the present invention provides a hydrophilic gel sustained release tablet containing echinacoside, comprising:
the solubilising chelating agent is selected from one or more of cyclodextrin and derivatives thereof.
Preferably, the solubilizing chelator is selected from one or more of hydroxypropyl-beta-cyclodextrin, sodium beta-cyclodextrin sulfobutyl ether.
Preferably, the mass ratio of the echinacoside to the solubilizing and chelating agent is 0.5-2:1.
Preferably, the release retarder is selected from one or more of methylcellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate and cellulose acetate phthalate;
the filler is one or more selected from lactose, starch, dextrin, calcium phosphate, calcium hydrogen phosphate and microcrystalline cellulose;
the glidant is one or more selected from silicon dioxide, magnesium stearate, talcum powder, calcium stearate, hard paraffin, zinc stearate, sodium stearate and sodium dodecyl sulfate.
Preferably, the release retarder is a compound release retarder selected from hydroxypropyl methylcellulose K15M and hydroxypropyl methylcellulose K4M;
the mass ratio of the hydroxypropyl methylcellulose K15M to the hydroxypropyl methylcellulose K4M is 1-7:1; preferably 2:1.
Preferably, the filler is selected from lactose and microcrystalline cellulose;
the mass ratio of lactose to microcrystalline cellulose is 1:0.75-4.
Preferably, the hydrophilic gel sustained release tablet containing echinacoside comprises:
the release retardant is selected from hydroxypropyl methylcellulose K15M and hydroxypropyl methylcellulose K4M;
the filler is selected from lactose and microcrystalline cellulose.
Preferably, the hydrophilic gel sustained release tablet containing echinacoside comprises:
preferably comprises:
the invention provides a preparation method of the hydrophilic gel sustained release tablet containing echinacoside, which comprises the following steps:
a) Mixing Echinacoside with the solubilization chelating agent solution, filtering, and drying to obtain solubilization chelating agent clathrate of Echinacoside;
b) Mixing the clathrate with release retardant and first filler, and granulating;
c) Mixing the obtained particles with a glidant and a second filler, and tabletting to obtain tablet cores;
d) Coating the tablet core to obtain the hydrophilic gel sustained-release tablet containing echinacoside.
The invention provides the hydrophilic gel sustained-release tablet containing the echinacoside or the application of the hydrophilic gel sustained-release tablet containing the echinacoside prepared by the preparation method in preparing medicines for preventing, alleviating or treating senile dementia.
Compared with the prior art, the invention provides a hydrophilic gel sustained release tablet containing echinacoside, which comprises the following components: 200-400 parts by weight of echinacoside; 200-400 parts by weight of solubilizing chelating agent; 300-600 parts by weight of release retarder; 100-180 parts of filler; 10-80 parts of glidant; 10-80 parts by weight of coating material; the solubilising chelating agent is selected from one or more of cyclodextrin and derivatives thereof.
The invention has the following beneficial effects:
1. in vitro experiments show that the sustained release preparation provided by the invention can be continuously and stably released within 24 hours, and provides a new choice for preventing and treating diseases such as senile dementia and the like.
2. Compared with the common tablet, the sustained-release preparation provided by the invention has reduced administration times and dosage.
3. The slow release preparation of the invention enhances the compliance of the related disease patients to take the medicine.
4. The sustained release preparation contains the solubilizing and chelating agent of the echinacoside, so that the water solubility of the raw material medicine is improved.
5. The slow release preparation contains a compound release retarder with synergistic effect, and achieves ideal slow release curve and clinical effect.
6. The slow release preparation of the invention improves the bioavailability of the medicine.
7. The slow release preparation is prepared by improving the dosage form of the constant release tablets of the echinacoside, and the developed hydrophilic gel slow release tablets of the echinacoside can be taken for 1-2 times a day, can reduce the fluctuation of blood concentration of the medicament in a human body, reduce toxic and side effects, improve the medication safety and enhance the curative effect of the echinacoside on diseases such as senile dementia and the like.
8. The sustained release tablet of the invention has simple preparation process and is beneficial to industrial production.
Detailed Description
The invention provides a hydrophilic gel sustained release tablet containing echinacoside, which comprises the following components:
the solubilising chelating agent is selected from one or more of cyclodextrin and derivatives thereof.
Aiming at the technical problems in the prior art, in order to reduce the administration frequency, reduce the fluctuation of the blood concentration of the medicine in the human body, reduce the toxic and side effects, avoid the phenomenon of missed administration of patients and improve the compliance of the patients, the invention designs the Echinacea purpurea glucoside hydrophilic gel skeleton sustained release tablet according to the principle of 'quality source design', and achieves the characteristic of 24-hour release. The sustained release tablet can provide proper blood concentration for human body in a preset period as required, reduce the administration times and obtain good therapeutic effect. Can maintain the blood concentration of human body for a long time, thereby avoiding the peak-valley phenomenon caused by frequent administration of the sustained-release preparation and improving the safety, the effectiveness and the adaptability of the medicine.
The content of the echinacoside is preferably 300-400 parts by weight, or preferably 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400 parts by weight, or any two end point values of the above ranges; further preferably 320 to 380 parts by weight, most preferably 360 parts by weight.
In the prescription design and preparation process of the pharmaceutical preparation, the invention adopts a medicine cyclodextrin inclusion/chelation technology, and a solubilizing chelant is added in the echinacoside hydrophilic gel sustained-release tablet, so that the water solubility of the active ingredient echinacoside is improved by forming the echinacoside-cyclodextrin chelate.
Preferably, the solubilization chelating agent is selected from one or more cyclodextrin derivatives such as hydroxypropyl-beta-cyclodextrin { HP-beta-CD }, beta-cyclodextrin sulfobutyl ether sodium { (SBE) 7 m-beta-CD }; sodium beta-cyclodextrin sulfobutyl ether is further preferred.
The content of the solubilizing and chelating agent is preferably 300 to 400 parts by weight, or preferably 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400 parts by weight, or a range between any two of the above endpoints; further preferably 320 to 380 parts by weight, most preferably 360 parts by weight.
The mass ratio of the echinacoside to the solubilizing and chelating agent is preferably 0.5-2:1, and more preferably 1:1.
Preferably, the release retarder comprises one or more of methylcellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate and cellulose acetate phthalate. Further preferred are the compound release retarders composed of hydroxypropyl methylcellulose K15M and hydroxypropyl methylcellulose K4M.
Preferably, the mass ratio of the hydroxypropyl methylcellulose K15M to the hydroxypropyl methylcellulose K4M is 1-7:1, more preferably 1-3:1, and most preferably 2:1.
In the prescription design and preparation process of the pharmaceutical preparation, the specific hydrophilic gel skeleton material is adopted as a release retarder for adjusting the release characteristic of the medicine. The hydrophilic gel skeleton material is hydrophilic polymer, and swells in water or digestive juice skeleton to form firm gel barrier to control medicine leaching and to protect the tablet core from being influenced by release medium to disintegrate. Over time, the outer gel layer dissolves continuously, the inner reformed gel layer resolubilizes until the tablet core is completely dissolved in the release medium.
The invention adopts the specific compound release retarder to exert the synergistic effect, so that the sustained-release preparation achieves a more ideal controlled-release effect.
In the present invention, the content of the release retarder is more preferably 375 to 525 parts by weight, still more preferably 400 to 500 parts by weight, or preferably 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500 parts by weight, or a range between any two of the above end points; most preferably 450 parts by weight.
The content of the hydroxypropyl methylcellulose K15M is preferably 250 to 350 parts by weight, more preferably 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350 parts by weight, or any two of the above ranges; most preferably 300 parts by weight.
The content of the hydroxypropyl methylcellulose K4M is preferably 50 to 250 parts by weight, more preferably 50, 70, 90, 110, 125, 150, 175, 200, 220, 250 parts by weight, or a range between any two of the above end values; most preferably 150 parts by weight.
Preferably, the filler comprises one or more of lactose, starch, dextrin, calcium phosphate, calcium hydrophosphate and microcrystalline cellulose, and more preferably lactose and microcrystalline cellulose.
The mass ratio of lactose to microcrystalline cellulose is preferably 1:0.75-4, more preferably 1:1-3, and most preferably 1:1.54.
In the present invention, the content of the filler is more preferably 100 to 180 parts by weight, still more preferably 130 to 160 parts by weight, and most preferably 132 parts by weight.
The lactose content is preferably 26 to 80 parts by weight, more preferably 26, 40, 50, 52, 60, 70, 80 parts by weight, or a range between any two of the above end points; most preferably 52 parts by weight.
The microcrystalline cellulose is preferably contained in an amount of 60 to 100 parts by weight, more preferably 60, 70, 74, 80, 90, 100 parts by weight, or a range between any two of the above end points; most preferably 80 parts by weight.
Lactose and microcrystalline cellulose are used as filling agents, so that the filling effect is achieved on one hand, the coordinated filling effect is achieved on the other hand, and the release effect is achieved by adjusting the dosage of the lactose and microcrystalline cellulose.
Preferably, the glidant comprises one or more of silicon dioxide, magnesium stearate, talcum powder, calcium stearate, hard paraffin, zinc stearate, sodium stearate and sodium dodecyl sulfate. Further preferred is silica or magnesium stearate.
The content of the glidant is more preferably 10 to 80 parts by weight, still more preferably 10 to 30 parts by weight, and most preferably 30 parts by weight.
The coating material of the present invention is not particularly limited, and suitable coating materials known to those skilled in the art, such as conventional sugar coating materials or enteric film coating materials, etc., may be used.
The content of the coating material is preferably 10 to 80 parts by weight, more preferably 10 to 30 parts by weight, and most preferably 30 parts by weight.
Preferably, the hydrophilic gel sustained release tablet containing echinacoside comprises:
the release retardant is selected from hydroxypropyl methylcellulose K15M and hydroxypropyl methylcellulose K4M;
the filler is selected from lactose and microcrystalline cellulose.
Preferably, the hydrophilic gel sustained release tablet containing echinacoside comprises:
more preferably, the hydrophilic gel sustained release tablet containing echinacoside comprises:
in the most preferred embodiment of the present invention, the hydrophilic gel sustained release tablet containing echinacoside comprises:
the preparation method of the hydrophilic gel sustained-release tablet containing echinacoside is not particularly limited, and the method can be applied by a person skilled in the art. Such as wet granulation, dry granulation tabletting or powder direct tabletting. Preferably, a wet granulation process is used.
Wherein wet granulation refers to a method of preparing granules by adding a liquid binder to a drug powder and agglomerating the powder together by bridging or bonding of the binder. Dry granulation is a process in which the drug powder is directly compressed into larger tablets or tablets and then re-crushed into granules of the desired size, without adding any liquid, and the binding force between the granules is mainly generated by the action of compression force. Powder direct compression refers to the direct compression of a drug powder with good compressibility and flowability into a hydrogel matrix tablet.
Preferably, the invention provides a preparation method of the hydrophilic gel sustained release tablet containing echinacoside, which comprises the following steps:
mixing Echinacoside with the solubilization chelating agent solution, filtering, and drying to obtain solubilization chelating agent clathrate of Echinacoside.
The mass ratio of the echinacoside to the solubilizing and chelating agent is preferably 1:1.
The above clathrate is then mixed with release retardant, first filler, and granulated.
And then mixing the obtained granules with a glidant and a second filler, and tabletting to obtain tablet cores.
Coating the tablet core to obtain the hydrophilic gel sustained-release tablet containing echinacoside.
The granulation is preferably wet granulation.
In some embodiments of the present invention, the preparation method specifically includes:
(1) Crushing Echinacoside, sieving with 100 mesh sieve, weighing according to the prescription, and mixing according to the weight ratio of 1: mixing the beta-cyclodextrin sulfobutyl ether sodium solution in proportion of 1, uniformly stirring, filtering, drying, and sieving with a 80-100 mesh sieve (preferably a 100 mesh pharmacopoeia sieve) to obtain an echinacoside-beta-cyclodextrin sulfobutyl ether sodium inclusion compound (marked as ECH- (SBE) 7 m-beta-CD, 1:1) for later use;
(2) Weighing the auxiliary materials according to the prescription proportion, fully mixing the raw materials with the release retardant and the first filler, adding 60% -80% (preferably 70%) of ethanol to prepare a soft material, and granulating by a 16-24 mesh sieve (preferably an 18-mesh pharmacopoeia sieve);
(3) Drying wet particles under the condition of 45-60 ℃ (preferably 50-60 ℃ and most preferably 55 ℃), finishing the dried wet particles by a 18-24 mesh sieve (preferably a 20 mesh pharmacopoeia sieve), adding a second filler and a glidant, and uniformly mixing;
(4) Checking the intermediate, calculating the center tablet weight and the tablet weight range of the tablet according to the particle content, and tabletting;
(5) Water is used as a solvent to prepare coating material coating liquid with the solid content of 8-15 percent, the tablet core of the sustained-release tablet is coated, and the coating weight is increased by about 2-5 percent;
(6) And (5) inspecting the finished product pieces, packaging after the inspection is qualified, and warehousing.
In a preferred embodiment of the present invention, the first filler is microcrystalline cellulose and the second filler is lactose.
Preferably, in the tabletting process, the rotating speed of the tablet press is set, parameters of the tablet press are adjusted, so that the tablet weight and hardness meet the requirements, namely the hardness is 40-100N, the tablet weight difference is +/-5.0%, the loss weight is not more than 1.0%, the content marking amount is 95-105%, the moisture content is less than or equal to 5%, the appearance shape is complete, black spots or color spots, broken edges and the like are not existed.
The coating materials and processes in the coating process are not particularly limited, and may be known to those skilled in the art.
The preparation method of the coating liquid is preferable: pouring the coating powder into the stirred water, and continuously stirring for 40-50 minutes to form a uniform dispersion, thus obtaining the coating powder with the preparation concentration of 8-15%.
Preferably, the coating method of the invention specifically comprises the following steps: placing a plain sheet with the hardness of more than or equal to 58N in a pot, enabling the pot to rotate, blowing hot air, preheating a sheet core to about 35-45 ℃, controlling the rotating speed of the pot, opening a spray gun, aligning the upper part of the turned sheet core, continuously spraying, increasing the spraying speed after a microfilm is formed on the surface of the sheet core, immediately stopping spraying if the sheet core is moist, and drying for a plurality of minutes. After spraying, the coating pot is slowly rotated for 3-5 min to dry the tablet core.
The invention provides the hydrophilic gel sustained-release tablet containing the echinacoside or the application of the hydrophilic gel sustained-release tablet containing the echinacoside prepared by the preparation method in preparing medicines for preventing, alleviating or treating senile dementia.
In order to further illustrate the present invention, the following describes in detail the present invention, the preparation method and application of the hydrophilic gel sustained release tablet containing echinacoside.
The technical guidelines of the pharmaceutical research of chemical oral sustained-release preparation indicate that: the design goal of the oral sustained release preparation is to delay the speed of releasing the medicine in the body so as to keep the blood concentration stable. The main drug release rate of the hydrophilic gel matrix sustained release tablet is affected by the type and the dosage of sustained release materials.
According to the physical and chemical properties of the echinacoside and the specific characteristics of different auxiliary materials, five prescription proportions are designed as follows, and the preparation process is as follows: crushing Echinacoside, preparing chelate, sieving with 100 mesh sieve, mixing with two kinds of hydroxypropyl methylcellulose, lactose and microcrystalline cellulose, wet granulating, drying, adding silicon dioxide, mixing, and tabletting.
Example 1
The preparation was carried out in the amounts indicated in Table 1 for prescription 1.
The preparation method comprises the following steps: pulverizing Echinacoside, preparing chelate, sieving, mixing with hydroxypropyl methylcellulose K15M, hydroxypropyl methylcellulose K4M, and microcrystalline cellulose, making soft mass, and granulating; drying, granulating, adding lactose and silicon dioxide, mixing, tabletting, and coating.
(1) Pulverizing 360 parts by weight of echinacoside, sieving with a 100-mesh pharmacopoeia sieve, weighing according to the prescription amount, and mixing according to the formula 1: mixing the beta-cyclodextrin sulfobutyl ether sodium solution with the proportion of 1, uniformly stirring, filtering, drying, and sieving through a 100-mesh pharmacopoeia sieve to obtain an echinacoside-beta-cyclodextrin sulfobutyl ether sodium inclusion compound (namely ECH- (SBE) 7 m-beta-CD, 1:1) for later use;
(2) Weighing auxiliary materials according to a prescription proportion, fully mixing the raw materials with 250 parts by weight of hydroxypropyl methylcellulose K15M, 125 parts by weight of hydroxypropyl methylcellulose K4M and 100 parts by weight of microcrystalline cellulose, adding 70% ethanol to prepare a soft material, and granulating by a 16-24 mesh sieve;
(3) Drying wet particles at 55 ℃, sieving the dried wet particles with a 20-mesh pharmacopoeia sieve, adding 82 parts by weight of lactose and 10 parts by weight of silicon dioxide, and uniformly mixing;
(4) Tabletting: setting the rotating speed of the tablet press, and adjusting parameters of the tablet press to enable the tablet weight and the hardness to meet the requirements, namely, the hardness is 40-100N, the difference of the tablet weights is +/-5.0%, the loss weight is not more than 1.0%, the content marking amount is 95-105%, the moisture content is less than or equal to 5%, the appearance shape is complete, black spots or color spots, broken edges and the like are not existed;
(5) Water is used as a solvent to prepare coating material coating liquid with the solid content of 8-15 percent, the tablet core of the sustained-release tablet is coated, and the coating weight is increased by about 2-5 percent;
(6) And (5) inspecting the finished product pieces, packaging after the inspection is qualified, and warehousing.
Example 2
The preparation was carried out in the amounts indicated in Table 1 for prescription 2.
The preparation method comprises the following steps: pulverizing Echinacoside, preparing chelate, sieving, mixing with hydroxypropyl methylcellulose K15M, hydroxypropyl methylcellulose K4M, and microcrystalline cellulose, making soft mass, and granulating; drying, granulating, adding lactose and silicon dioxide, mixing, tabletting, and coating.
The specific process parameters were the same as in example 1.
Example 3
The preparation was carried out in the amounts indicated in Table 1 for prescription 3.
The preparation method comprises the following steps: pulverizing Echinacoside, preparing chelate, sieving, mixing with hydroxypropyl methylcellulose K15M, hydroxypropyl methylcellulose K4M, and microcrystalline cellulose, making soft mass, and granulating; drying, granulating, adding lactose and silicon dioxide, mixing, tabletting, and coating.
The specific process parameters were the same as in example 1.
Example 4
The preparation was carried out in the amounts indicated in Table 1 for prescription 4.
The preparation method comprises the following steps: pulverizing Echinacoside, preparing chelate, sieving, mixing with hydroxypropyl methylcellulose K15M, hydroxypropyl methylcellulose K4M, and microcrystalline cellulose, making soft mass, and granulating; drying, granulating, adding lactose and silicon dioxide, mixing, tabletting, and coating.
The specific process parameters were the same as in example 1.
Example 5
The preparation was carried out in the amounts indicated in Table 1 for prescription 5.
The preparation method comprises the following steps: pulverizing Echinacoside, preparing chelate, sieving, mixing with hydroxypropyl methylcellulose K15M, hydroxypropyl methylcellulose K4M, and microcrystalline cellulose, making soft mass, and granulating; drying, granulating, adding lactose and silicon dioxide, mixing, tabletting, and coating.
The specific process parameters were the same as in example 1.
Comparative example 1
The preparation method differs from the preparation method of example 3 in that: pulverizing 360 parts by weight of echinacoside, sieving with a 100-mesh sieve, mixing with 300 parts by weight of hydroxypropyl methylcellulose K15M, 150 parts by weight of hydroxypropyl methylcellulose K4M, 52 parts by weight of lactose and 80 parts by weight of microcrystalline cellulose, granulating with 70% ethanol by wet method, drying at 55 ℃, adding 30 parts by weight of silicon dioxide, uniformly mixing, and tabletting.
Comparative example 2
The preparation method differs from the preparation method of example 3 in that: pulverizing 360 parts by weight of echinacoside, sieving with a 100-mesh sieve to prepare chelate, mixing with 300 parts by weight of hydroxypropyl methylcellulose K15M, 52 parts by weight of lactose and 80 parts by weight of microcrystalline cellulose, granulating with 70% ethanol by a wet method, drying at 55 ℃, adding 30 parts by weight of silicon dioxide, uniformly mixing, and tabletting.
Comparative example 3
The preparation method differs from the preparation method of example 3 in that: pulverizing 360 parts by weight of echinacoside, sieving with a 100-mesh sieve to prepare chelate, mixing with 150 parts by weight of hydroxypropyl methylcellulose K4M, 52 parts by weight of lactose and 80 parts by weight of microcrystalline cellulose, granulating with 70% ethanol by a wet method, drying at 55 ℃, adding 30 parts by weight of silicon dioxide, uniformly mixing, and tabletting.
Comparative example 4
The raw materials used were the same as in prescription 3, and the preparation method was different from that of example 3 in that: pulverizing 360 parts by weight of echinacoside, sieving with a 100-mesh sieve to prepare chelate, sieving, uniformly mixing with 300 parts by weight of hydroxypropyl methylcellulose K15M, 150 parts by weight of hydroxypropyl methylcellulose K4M, 52 parts by weight of lactose, 80 parts by weight of microcrystalline cellulose and 30 parts by weight of silicon dioxide, and directly tabletting.
Comparative example 5
The Echinacoside sustained release tablet is prepared by taking Echinacoside, adding filler, adding appropriate amount of disintegrating agent, adding appropriate amount of lubricant, and tabletting. The relevant prescription proportion is as follows: 40 parts of echinacoside, 49 parts of microcrystalline cellulose, 10.5 parts of croscarmellose sodium, 2 parts of sodium carboxymethylcellulose and 0.5 part of magnesium stearate.
Table 1 composition of the Echinacoside sustained release tablet by prescription screening
According to the physicochemical properties of the echinacoside and the specific characteristics of different auxiliary materials, comparing and inspecting the indexes such as the dried granule condition, the tablet appearance, the hardness, the release degree and the like, determining the optimal prescription, and the result is shown in the following table 2:
TABLE 2 granule conditions, tablet appearance, hardness and Release
The release degree measuring method comprises the following steps: taking the product, taking a release degree measuring method (four parts of Chinese pharmacopoeia 2020 edition), adopting a release degree measuring device, taking distilled water as a release medium, operating according to the method, taking proper amounts of release liquid respectively after 1, 3, 9, 12 and 18 hours, supplementing the release medium with the same temperature and the same volume at the same time, filtering, precisely measuring 20 mu L of the continuous filtrate according to chromatographic conditions under the content measuring item, and recording a chromatogram; and taking an appropriate amount of echinacoside reference substance, precisely weighing, using the reference substance as a standard solution, measuring by the same method, and calculating the release amount of each tablet at different time points. The release amount of each tablet in 3, 9, 12 and 18 hours should be 30% below, 30% -60%, 40% -70% and 80% above of the marked amount respectively, and all should meet the regulations.
Taking 3 tablets of the product, measuring the release degree of the product according to the method, sampling and measuring the release degree after 1, 3, 9, 12 and 18 hours respectively, and comparing the measurement results of the release degrees of the samples with the following table 3:
TABLE 3 Release degree
As is clear from the test results, the dry pellets prepared in example 2 and example 4 were inferior in flowability, and it was difficult to press a sheet having a preferable sheet weight and hardness due to a small bulk density. From the results of the release measurement, the release of the embodiment 1 is faster, and the embodiment 2, the embodiment 3, the embodiment 4 and the embodiment 5 are more ideal, and the release characteristics of the conventional sustained release tablets are met. In summary, the formulation of example 3 is preferred as a core formulation of the sustained-release Echinacoside tablet, in combination with factors such as fluidity of the granules, ease of tabletting, and cost of production.
The above description of the embodiments is only for aiding in the understanding of the method of the present invention and its core ideas. It should be noted that it will be apparent to those skilled in the art that various modifications and adaptations of the invention can be made without departing from the principles of the invention and these modifications and adaptations are intended to be within the scope of the invention as defined in the following claims.
Claims (11)
1. A hydrophilic gel sustained release tablet containing echinacoside, comprising:
200-400 parts of echinacoside;
200-400 parts by weight of a solubilizing chelating agent;
300-600 parts by weight of release retarder;
100-180 parts of filler;
10-80 parts of a glidant;
10-80 parts by weight of a coating material;
the solubilizing chelating agent is selected from one or more of cyclodextrin and derivatives thereof;
the release retarder is a compound release retarder and is selected from hydroxypropyl methylcellulose K15M and hydroxypropyl methylcellulose K4M;
the mass ratio of the hydroxypropyl methylcellulose K15M to the hydroxypropyl methylcellulose K4M is 1-7:1.
2. The hydrophilic gel sustained-release tablet containing echinacoside according to claim 1, wherein said solubilizing chelating agent is selected from one or more of hydroxypropyl- β -cyclodextrin, sodium β -cyclodextrin sulfobutyl ether.
3. The hydrophilic gel sustained-release tablet containing echinacoside as claimed in claim 1, wherein the mass ratio of the echinacoside to the solubilizing and chelating agent is 0.5-2:1.
4. The hydrophilic gel sustained-release tablet containing echinacoside according to claim 1, wherein the filler is one or more selected from lactose, starch, dextrin, calcium phosphate, calcium hydrogen phosphate, microcrystalline cellulose;
the glidant is one or more selected from silicon dioxide, magnesium stearate, talcum powder, calcium stearate, hard paraffin, zinc stearate, sodium stearate and sodium dodecyl sulfate.
5. The hydrophilic gel sustained-release tablet containing echinacoside according to claim 1, wherein the mass ratio of hydroxypropyl methylcellulose K15M to hydroxypropyl methylcellulose K4M is 2:1.
6. The hydrophilic gel sustained-release tablet containing echinacoside according to claim 1, wherein said filler is selected from lactose and microcrystalline cellulose;
the mass ratio of lactose to microcrystalline cellulose is 1:0.75-4.
7. The hydrophilic gel sustained-release tablet containing echinacoside as claimed in claim 1, comprising:
200-400 parts of echinacoside;
200-400 parts by weight of beta-cyclodextrin sulfobutyl ether sodium;
300-600 parts by weight of release retarder;
100-180 parts of filler;
10-80 parts of a glidant;
10-80 parts by weight of a coating material;
the release retardant is selected from hydroxypropyl methylcellulose K15M and hydroxypropyl methylcellulose K4M;
the filler is selected from lactose and microcrystalline cellulose.
8. The hydrophilic gel sustained-release tablet containing echinacoside as claimed in claim 1, comprising:
360 parts of echinacoside;
360 parts by weight of beta-cyclodextrin sulfobutyl ether sodium;
250-350 parts by weight of hydroxypropyl methylcellulose K15M;
50-250 parts by weight of hydroxypropyl methylcellulose K4M;
60-100 parts by weight of microcrystalline cellulose;
26-80 parts of lactose;
10-30 parts of silicon dioxide;
30 parts of coating material.
9. The hydrophilic gel sustained-release tablet containing echinacoside as claimed in claim 8, comprising:
360 parts of echinacoside;
360 parts by weight of beta-cyclodextrin sulfobutyl ether sodium;
hydroxypropyl methylcellulose K15M 300 parts by weight;
150 parts by weight of hydroxypropyl methylcellulose K4M;
80 parts by weight of microcrystalline cellulose;
52 parts by weight of lactose;
30 parts by weight of silicon dioxide;
30 parts of coating material.
10. The method for preparing the echinacoside-containing hydrophilic gel sustained-release tablet according to any one of claims 1 to 9, comprising:
a) Mixing Echinacoside with the solubilization chelating agent solution, filtering, and drying to obtain solubilization chelating agent clathrate of Echinacoside;
b) Mixing the clathrate with release retardant and first filler, and granulating;
c) Mixing the obtained particles with a glidant and a second filler, and tabletting to obtain tablet cores;
d) Coating the tablet core to obtain the hydrophilic gel sustained-release tablet containing echinacoside.
11. Use of a Echinacoside-containing hydrophilic gel sustained-release tablet according to any one of claims 1 to 9 or a Echinacoside-containing hydrophilic gel sustained-release tablet prepared by the preparation method according to claim 10 in the preparation of a medicament for preventing, alleviating or treating senile dementia.
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| CN101259134B (en) * | 2005-01-28 | 2011-05-25 | 北京华医神农医药科技有限公司 | New pharmaceutical use of echinacoside |
| CN100387235C (en) * | 2005-01-28 | 2008-05-14 | 北京华医神农医药科技有限公司 | New pharmaceutical use of echinacoside |
| CN101766694A (en) * | 2008-12-26 | 2010-07-07 | 北京琥珀光华医药科技开发有限公司 | Process for extracting total glucosides from desertliving cistanche and preparation thereof |
| CN101518519A (en) * | 2009-04-03 | 2009-09-02 | 中山大学 | Naringin slow-release tablet and method for preparing same |
| CN102283855A (en) * | 2011-09-13 | 2011-12-21 | 中国农业大学 | Application of echinacoside to preparation of medicament for treating inflammatory bowel diseases |
| WO2015171977A1 (en) * | 2014-05-08 | 2015-11-12 | Access Business Group International Llc | Method for improving memory of a subject using a composition comprising cistanche and ginkgo extracts |
| CN106038646A (en) * | 2016-05-11 | 2016-10-26 | 南京泽朗医药科技有限公司 | A method of preparing an echinacea purpurea extract product and applications of the extract product |
| CN109908272A (en) * | 2019-03-01 | 2019-06-21 | 深圳海王医药科技研究院有限公司 | A kind of day silver-colored desert cistanche piece and preparation method thereof |
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| CN104605348A (en) * | 2015-01-09 | 2015-05-13 | 北京博远欣绿科技股份有限公司 | Healthcare product containing cistanche tubulosa extract and preparation method thereof |
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