CN1682730A - Cepharanthine slow releasing preparation - Google Patents

Abstract

The present invention relates to a kind of slow releasing cepharanthine preparation. The preparation includes cepharanthine and pharmaceutically acceptable release delaying supplementary material in the weight ratio of 2-8 to 1-7. The slow releasing preparation includes skeleton type slow releasing preparation, film controlled slow releasing preparation, penetrating pump type slow releasing preparation and slow releasing preparation prepared with microcapsule, microballoon or pill. The slow releasing cepharanthine preparation has prolonged medicine action time, reduced taking times, reduced side effect of medicine and raised medicine compliance, and is safe, effective and reliable.

Description

Stephanie Sustained Release Preparation

technical field

The invention relates to a pharmaceutical preparation, in particular to a stepherin preparation.

Background technique

Cepharanthine (Ceph) is an alkaloid extracted from Stephiania japonica (Thunb.) Miers. It is a beige powder with a molecular formula of C ₃₇ H ₃₈ N ₂ O ₆ and a molecular weight of 606.686. Drug-induced leukopenia, anti-inflammation, anti-hemolysis, enhanced immunity, promotion of radiation-irradiated mouse antibody production, anti-tumor, analgesia, membrane stabilization, inhibition of platelet aggregation, inhibition of phosphodiester ester activity, treatment of silicosis and reduction in rats Peritoneal white blood cells release arachidonic acid and leukotriene B4 and so on.

At present, the domestically-developed and clinically-applied Stephalin Tablets contain 20mg Stephanitin, and the dosage is 1 tablet each time, 3 times a day, and each course of treatment is 1-2 months. The number of daily oral administration is large, the course of treatment is long, and it is troublesome for patients to take it. It is prone to missed doses and the interval between nightly doses is too long to maintain effective blood drug concentration and exert a sustained therapeutic effect, resulting in blind spots in treatment.

Therefore, if a new, convenient, effective, and long-acting drug release system is developed to release the drug continuously, stably and quantitatively in a longer period of time, so that the patient only takes it once a day, it can be avoided. The generation of above-mentioned unfavorable factors, and can produce very beneficial effect to doctor, nurse, patient.

Contents of the invention

The object of the present invention is to provide a kind of stepherin sustained-release preparation. The stephatrin sustained-release preparation uses different drug release mechanisms to prolong the action time, reduce the number of times of taking the medicine, reduce the side effects of the medicine and improve the patient's medication compliance.

According to the purpose of the present invention, the present invention provides a kind of stepahelin sustained-release preparation, which preparation comprises

Stephania; and

Pharmaceutically acceptable excipients for sustained release;

The weight ratio of the two is 2-8:1-7.

Preferably, the sustained-release preparation comprises the following ingredients by weight percentage:

Stephaniacine 20-80%;

Excipients with sustained release effect 10-70%;

Other accessories 0～70%;

The other auxiliary materials are selected from plasticizers, lubricants, binders, solvents and excipients.

Wherein, plasticizer can adopt glycerin, castor oil, polyethylene glycol etc.;

Adhesives can use polyvinylpyrrolidone, sodium carboxymethyl cellulose, methyl cellulose, ethyl cellulose, starch slurry, etc.;

Lubricants can be magnesium stearate, talcum powder, liquid paraffin, colloidal silicon dioxide;

The solvent can be ethanol, water, acetone, methanol, chloroform, etc.;

Excipients can be dextrin, starch, lactose, microcrystalline cellulose and the like.

The stepherin sustained-release preparations include matrix-type sustained-release preparations, membrane-controlled sustained-release preparations, osmotic pump-type sustained-release preparations, and slow-release preparations made into microcapsules, microspheres, and pellets.

The adjuvant for sustained release is a skeleton material and/or a coating material, that is, the two materials can be used alone or in combination.

The skeleton material is selected from cellulose derivatives, acrylic resins, vinyl polymers and other auxiliary materials.

Wherein, the cellulose derivatives are one or more selected from ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, and sodium carboxymethyl cellulose;

The acrylic resins are acrylic resin II and/or acrylic resin III;

The vinyl polymers are one or more selected from polyvinylpyrrolidone, polyvinyl alcohol, polystyrene, polyvinyl chloride;

The other auxiliary materials are one or more selected from stearyl alcohol, chitin, stearic acid, polyethylene glycol, gelatin, mannitol, and sorbitol.

The coating material is selected from cellulose esters, cellulose ethers, esters of cellulose ethers, acrylic acid homopolymers and copolymers, and natural medicinal polymer materials.

Wherein, the cellulose esters are cellulose acetate and/or cellulose acetate butyrate;

The cellulose ethers are hydroxypropyl methylcellulose;

The esters of the cellulose ethers are hydroxypropyl methylcellulose phthalate;

The acrylic homopolymer and copolymer are one or more selected from acrylic resin series, for example, acrylic resin No. I, acrylic resin No. II, acrylic resin No. III, etc.

The natural medicinal polymer material is chitin and/or chitosan.

The dosage form of the stephandin sustained-release preparation of the present invention is mainly tablets, and may also be pills, granules and the like.

The unit dosage form of the sustained-release preparation of echinacea can contain 40 mg to 400 mg of echinacea, and the number of daily administrations is reduced from three times for common preparations to one time. In a specific embodiment of the present invention, the unit dosage form of the stepherin sustained-release preparation contains 60 mg of stepherin.

The stepherin sustained-release preparation of the present invention can be prepared by conventional methods in the art.

For example: mix stephatrin with skeleton material, add binder to granulate, add lubricant and directly compress into tablets.

Another example: mix paternal vine with skeleton material or paternal vine with excipients, add binder to make drug core, granules, pills, tablets, etc., and then coat them.

The results of the in vitro release test show that the stephenicine sustained-release tablet provided by the present invention gradually releases the drug within 12 hours to maintain the blood drug concentration required for treatment, thereby reducing the number of times of taking and lasting effect compared with ordinary tablets. For the purpose of convenience.

In order to better understand the essence of the present invention, the following describes the preferred embodiments of the present invention in detail but does not limit the present invention.

Detailed ways

The test materials used in the present invention are all commercially available products unless otherwise specified.

Preparation of Paternausin Sustained-release Preparation

【Example 1】

I prescription

Phalaenopsis 100mg

Hydroxypropyl Methyl Cellulose 50mg

Lactose 20mg

Magnesium stearate 10mg

Microcrystalline Cellulose 30mg

II preparation method

Mix stephatrin and microcrystalline cellulose for 10 minutes, add hydroxypropyl methylcellulose (HPMC) and lactose, mix well, dissolve in ethanol to make a soft material, granulate, dry, granulate, and harden Magnesium steatate was mixed evenly, and tabletted to obtain pachyphyllin sustained-release tablets.

[Example 2]

I prescription

Phalaenopsis 60mg

Hydroxypropyl Methyl Cellulose 12mg

Dextrin 4mg

Magnesium stearate 5mg

II preparation method

Mix patinol with hydroxypropyl methylcellulose and dextrin, make soft material, granulate with a 20-mesh sieve, dry, granulate with 18 mesh, add magnesium stearate, mix well, and tablet Sustained Release Tablets.

[Example 3]

I prescription

Phalaenopsis 200mg

Stearic acid 15mg

Ethylcellulose 50mg

Magnesium Stearate 10mg

II preparation method

Mix patinol and stearic acid, add 10% ethyl cellulose ethanol solution to granulate, dry, add magnesium stearate, mix evenly, granulate, and compress into tablets to obtain paternil slow-release tablets.

【Example 4】

I prescription

Chip

Phalaenopsis 400mg

Lactose 40mg

Ethylcellulose 10mg

Magnesium Stearate 20mg

Coating solution

Cellulose acetate 10g

Polyethylene glycol 400 15ml

Acetone 100ml

II preparation method

Mix pachyphyllin and lactose evenly, add ethyl cellulose ethanol liquid to make soft material, pass through a 16-mesh sieve to make wet granules, dry, pass through a 14-mesh sieve to granulate, add magnesium stearate and mix well, then compress into tablets, pack Clothes, laser drilling, that is stephaniacine slow-release tablets.

【Example 5】

I prescription

Chip

Phalaenopsis 100mg

Mannitol 10mg

Magnesium stearate 1mg

Coating solution

Phalaenopsis 20mg

Cellulose acetate 30mg

Add acetone to 25ml

II preparation method

Mix stepherin and mannitol evenly, add water to make granules, dry, granulate, add magnesium stearate and mix evenly, then compress into tablets, spray coat with acetone aqueous solution containing stepherin and cellulose acetate, dry, and laser Punch the holes to get the stephensu sustained-release tablets.

[Example 6]

I prescription

Chip

Phalaenopsis 200mg

Ethylcellulose 55mg

Magnesium stearate 3mg

Coating solution

Cellulose diacetate 3g

Macrogol 400 2.5ml

Diethyl phthalate 2.5ml

Acetone Add 25ml

II preparation method

Take the main drug and auxiliary materials, mix well, add adhesive, make soft material, pass through 20-mesh nylon sieve to make wet granules, dry, sieve and granulate, compress into tablets, and coat ie stephin sustained-release tablets.

[Example 7]

I prescription

Ball core

Phalaenopsis 100mg

Starch 40mg

Dextrin 45mg

Coating solution

Acrylic resin No. II 1.5g

Polyethylene glycol 400 3ml

Diethyl phthalate 0.01g

Appropriate amount of talcum powder

Add ethanol to 25ml

II preparation method

Thoroughly mix Stephaniacine with appropriate proportions of starch and dextrin, use a certain concentration of ethanol in a coating pan to make pellet cores, take them out, and dry them. Take the dried pellet core, weigh it after removing the fine powder, put it in the coating pan and coat it, and then obtain the stephenicin controlled-release pellets, which can be further processed into other dosage forms.

Study on the in vitro release rate of paternogenin sustained-release preparation

[Embodiment 8]

Get Stephanie Sustained-release Tablets A, B, C (prepared according to Examples 1, 2, and 6 respectively), Stephanitin Common Tablets (20 mg per tablet, Guiyang Jinqiao Pharmaceutical Factory) each six, 900ml 0.1mol/ L HCl solution as solvent, temperature 37°C, rotation speed 100r/min, sample 5ml at fixed points at 1, 2, 4, 6, 8, 10, and 12 hours respectively (add 5ml of the same medium at the same time), 0.45μm microporous membrane Filtration, high performance liquid phase method to determine the cumulative drug release, and calculate the relative cumulative drug release percentage. In this test, the release uniformity and reproducibility were good. Table 1 shows the comparison results of the average cumulative drug release rate of Stephalin Sustained-release Tablets and Stephanitin Ordinary Tablets.

The test results show that the average cumulative drug release rate of ordinary tablets has exceeded 80% in 1 hour, and the drug release amount has little change thereafter, while the drug release effect of sustained-release tablets is obvious. The drug release curve in 12 hours fits the Higuchi equation, and the average The cumulative drug release rate can reach more than 90%. The stephenicine sustained-release tablet of the present invention gradually releases the drug within 12 hours to maintain the blood drug concentration required for treatment, so as to achieve the purposes of reducing the number of times of taking, lasting effect and being convenient to take.

Table 1 Comparison of the average cumulative drug release percentages of stephadin sustained-release tablets and stephadin ordinary tablets (n=6) time (hours) 1 2 4 6 8 10 12 Ordinary film (%) 82.37 83.17 84.14 84.16 84.20 84.22 84.25 Sustained-release tablet A(%) 18.21 26.89 48.79 56.98 84.67 88.75 91.20 Sustained-release tablet B(%) 20.30 31.51 56.72 63.42 84.28 90.45 92.83 Sustained-release tablet C(%) 22.56 32.42 61.23 75.54 80.25 91.23 93.41

The above description of the preferred embodiments of the present invention does not limit the present invention, and those skilled in the art can make various changes or deformations according to the present invention, as long as they do not depart from the spirit of the present invention, all should belong to the scope of the appended claims of the present invention.

Claims (7)

1. A stepahelin slow-release preparation, characterized in that it contains Stephania; and Pharmaceutically acceptable excipients for sustained release; The weight ratio of the two is 2-8:1-7. 2. The paternogenin sustained-release preparation according to claim 1, characterized in that it comprises the following components by weight percentage: Stephaniacine 20-80%; Excipients with sustained release effect 10-70%; Other accessories 0～70%; The other auxiliary materials are selected from plasticizers, lubricants, binders, solvents and excipients. 3. The sustained-release preparation of phaegnathin according to claim 2, characterized in that the adjuvant that plays a role in sustained release is a skeleton material and/or a coating material. 4. The stephenicine slow-release preparation according to claim 3, characterized in that The skeleton material is selected from cellulose derivatives, acrylic resins, vinyl polymers and other auxiliary materials; Wherein, the cellulose derivatives are one or more selected from ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, and sodium carboxymethyl cellulose; The acrylic resin is No. II acrylic resin and/or No. III acrylic resin; The vinyl polymers are one or more selected from polyvinylpyrrolidone, polyvinyl alcohol, polystyrene, polyvinyl chloride; The other auxiliary materials are one or more selected from octadecyl alcohol, chitin, stearic acid, polyethylene glycol, gelatin, mannitol, and sorbitol; The coating material is selected from cellulose esters, cellulose ethers, esters of cellulose ethers, acrylic acid homopolymers and copolymers, and natural medicinal polymer materials; Wherein, the cellulose esters are cellulose acetate and/or cellulose acetate butyrate; The cellulose ethers are hydroxypropyl methylcellulose; The esters of the cellulose ethers are hydroxypropyl methylcellulose phthalate; The acrylic homopolymer and copolymer are one or more of acrylic resin No. I, acrylic resin No. II, and acrylic resin No. III; The natural medicinal polymer material is chitin and/or chitosan. 5. The stepherin sustained-release preparation according to any one of claims 1-4, characterized in that the unit dosage form of the stepherin sustained-release preparation contains 40 mg-400 mg of stepherin. 6. The paternogenin sustained-release preparation according to claim 5, characterized in that its unit dosage form contains the following components: Phalaenopsis 60mg Hydroxypropyl Methyl Cellulose 12mg Dextrin 4mg Magnesium stearate 5mg 7. The preparation method of the stephatrin sustained-release preparation according to claim 6, characterized in that the stephatrin is mixed with hydroxypropyl methylcellulose and dextrin to make a soft material, granulated with a 20-mesh sieve, and dried. The 18-mesh whole grain is added with magnesium stearate, mixed evenly, and compressed into tablets.