CN113813223A - Micro suppository and composition and preparation method thereof - Google Patents

Micro suppository and composition and preparation method thereof Download PDF

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Publication number
CN113813223A
CN113813223A CN202111257827.7A CN202111257827A CN113813223A CN 113813223 A CN113813223 A CN 113813223A CN 202111257827 A CN202111257827 A CN 202111257827A CN 113813223 A CN113813223 A CN 113813223A
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China
Prior art keywords
suppository
micro
composition
weight
parts
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CN202111257827.7A
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Chinese (zh)
Inventor
全丹毅
张双双
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Jiangsu Jicui New Pharmaceutical Preparation Technology Research Institute Co ltd
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Jiangsu Jicui New Pharmaceutical Preparation Technology Research Institute Co ltd
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Priority to CN202111257827.7A priority Critical patent/CN113813223A/en
Publication of CN113813223A publication Critical patent/CN113813223A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/606—Salicylic acid; Derivatives thereof having amino groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
    • A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0031—Rectum, anus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0046—Ear

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Abstract

The invention relates to the field of medicinal preparations, in particular to a micro-suppository composition, a micro-suppository containing the composition or prepared from the composition, and a capsule preparation containing the micro-suppository and used for cavity administration. The composition comprises a matrix group and an optional drug group; wherein the matrix group comprises an oil-soluble matrix and a water-soluble matrix, and the weight ratio of the oil-soluble matrix to the water-soluble matrix is 1: (0.2-5). The capsule preparation prepared from the micro-suppository composition does not cause a flow-off phenomenon after administration, can flexibly adjust the dosage and the drug release speed, and has very high drug-loading rate.

Description

Micro suppository and composition and preparation method thereof
Technical Field
The invention relates to the field of medicinal preparations, in particular to a micro-suppository composition, a micro-suppository containing the composition or prepared from the composition, a preparation method of the micro-suppository and a capsule preparation containing the micro-suppository for cavity administration.
Background
The cavity administration is an administration way which can play a role in local and systemic treatment, has high safety and high patient adaptability, is suitable for people of all ages, and has extremely wide prospect application. The cavity administration mainly comprises rectal administration, vaginal administration, urethral administration, nasal administration, auditory canal administration and the like.
The common dosage form for the cavity administration is suppository. The suppository mainly has the shapes of a cone, a cylinder, a torpedo and the like, each suppository is about 2-4g in weight, 3-4 cm in length and 1-2cm in width, and after being placed in a cavity, a patient is easy to feel foreign body due to the large volume of the suppository, most of the suppository adopts an oil-soluble matrix, and the oil-soluble matrix is rapidly melted after entering the cavity, so that leakage is caused, and the acceptance of the patient is not high. In addition, the suppository is usually prepared by a hot melting method, namely, the matrix is heated and melted and then mixed with the medicament, homogenized, injected, cooled, strickled, demoulded and packaged, the process is complex, a dual-phase medicament release unit is difficult to prepare, and the condition of uneven dispersion of the medicament and the matrix is easy to occur in the preparation process. The common suppository prepared by the prior art has the drug-loading rate generally not more than 20 percent and can not achieve satisfactory treatment effect.
Therefore, it is very important to provide a novel sustained release preparation for cavity administration.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a micro-suppository composition, a micro-suppository containing the composition or prepared from the composition, a preparation method of the micro-suppository and a capsule preparation containing the micro-suppository for cavity administration. The capsule preparation prepared from the micro-suppository composition does not cause a flow-off phenomenon after administration, can flexibly adjust the dosage and the drug release speed, and has very high drug-loading rate.
The inventors of the present invention have found that the problems of easy leakage, uneven distribution of drug and low drug loading rate of the prior art suppository for cavity administration are mainly due to the limitation of the current conventional process. The inventors of the present invention have creatively contemplated that hot melt extrusion processes used in other areas may be applied to suppository preparation.
Therefore, the inventor of the invention improves the medicament formula, and the oil-soluble matrix and the water-soluble mechanism are matched in a specific ratio, so that the mixed matrix not only can be suitable for a hot-melt extrusion process, but also has the advantages of the oil-soluble matrix and the water-soluble matrix in a breakthrough manner, thereby improving the bioavailability of the medicament and enabling the loading of the medicament with large dose to be possible. The micro suppository obtained by the hot melt extrusion process can be very conveniently filled into capsule shells with various sizes, so that various micro suppositories with different medicament contents, different formulas and different medicament selections can be flexibly mixed and filled into one capsule shell, the melting rate of the micro suppository in the body and the release of the medicament can be flexibly adjusted, specific, different and staged clinical requirements are met, more choices are provided for doctor to dispense, new possibilities are provided for dispensing modes, and the micro suppository has wide application prospects and can be suitable for medicament dispensing of the old, children and pets.
In order to achieve the above objects, the present invention provides in a first aspect a composition for a micro-suppository, wherein the composition comprises a base group and optionally a drug group; wherein the matrix group comprises an oil-soluble matrix and a water-soluble matrix, and the weight ratio of the oil-soluble matrix to the water-soluble matrix is 1: (0.2-5).
Preferably, the oil-soluble base is selected from one or more of cocoa butter, semisynthetic fatty acid glycerides, lanolin, allspice butter, and derivatives thereof.
Preferably, the water soluble matrix is selected from one or more of gelatin, polyethylene glycol and derivatives thereof.
Preferably, the weight ratio of the oil-soluble matrix to the water-soluble matrix is 1: (0.5-3).
Preferably, the matrix set comprises one or more of the following combinations: cocoa butter and gelatin in a weight ratio of 1: (0.8-2), semisynthetic fatty acid and polyethylene glycol in a weight ratio of 1: (2-2.5).
Preferably, the matrix group is contained in an amount of 30 to 500 parts by weight, more preferably 50 to 250 parts by weight, relative to 100 parts by weight of the drug group; more preferably 50 to 150 parts by weight.
The drug group may not be included in the composition of the present invention. It will be appreciated that although the final medicament is necessarily a drug, it is not necessary to prepare the drug at the same time as the preparation of the starting material, and therefore the composition of the invention need not include a drug for ease of manufacture and sale. It will also be appreciated that the absence of a drug in the composition is based on the need for manufacturing, shipping and marketing, and that the other ingredients in the composition may be present in a range suitable for the drug present in the composition, not conflicting with the absence of a drug in the composition, based on the need for the final pharmaceutical product to perform better.
It will be appreciated that the inventive concept of the present invention is not much related to the specific choice of drugs, and that various drugs can be used in the present invention with good results, and therefore the present invention does not require the choice of drugs. For example only, the drug of the present invention may be, for example, mesalamine, aspirin, chlorhexidine acetate, danazol, ketoprofen, naproxen, erythromycin, and the like.
Preferably, the composition further comprises an absorption interfering group comprising an absorption enhancer and/or an absorption blocker.
The absorption interference group can only comprise the absorption enhancer, can also comprise the absorption retarder, and can also comprise the absorption enhancer and the absorption retarder at the same time.
Preferably, the content of the absorption interfering group is 0 to 80 parts by weight, more preferably 10 to 40 parts by weight, and still more preferably 20 to 30 parts by weight, relative to 100 parts by weight of the drug group.
Preferably, the absorption enhancer is selected from one or more of laurocapram, salicylic acid, sodium bicarbonate, urea, beta 2 cyclodextrin, N2 acylamino acid, adipic acid and derivatives thereof; further preferred is one or more of laurocapram, salicylic acid, urea, and N2 acylamino acid.
Preferably, the absorption retardant is selected from one or more of natural soybean phospholipids, hydrogenated soybean phospholipids, alginic acid, stearic acid, beeswax and hydroxypropylmethyl cellulose; preferably one or more of hydrogenated soybean phospholipids, alginic acid and beeswax.
According to a particular embodiment, the absorption enhancer is laurocapram and urea in a weight ratio of 1: (0.2-0.6), more preferably 1: (0.3-0.5).
According to a preferred embodiment, the composition of the invention further comprises a surfactant.
The surfactant may be one or more of span and Tween, which are conventional in the art.
Preferably, the surfactant is contained in an amount of 5 to 50 parts by weight, more preferably 15 to 25 parts by weight, relative to 100 parts by weight of the drug group.
Under the condition of no special requirement, the micro suppository of the invention only contains a medicine group and a matrix group, and under the condition of not adding an absorption interference agent and/or a surfactant, the micro suppository of the invention can be well molded and can be effectively absorbed and utilized, so that the drug loading rate is further improved. The drug loading of the invention can even reach 70%.
In the present invention, if necessary, the composition may further include an auxiliary material. The excipients may be selected, for example, from one or more of diluents, lubricants and bacteriostats, as well as other excipients conventional in the art.
The content of the adjuvant may be 5 to 100 parts by weight, preferably 10 to 30 parts by weight, with respect to 100 parts by weight of the pharmaceutical composition.
The micro suppository can realize better effect without adding auxiliary materials.
In a second aspect, the present invention provides a micro-suppository, wherein the composition according to the first aspect is contained in the micro-suppository or is prepared from the composition.
The size of the micro-suppositories can be obtained by cutting and can therefore be adjusted within a wide range.
The shape of the micro-suppository is not limited either, and may be a tablet type, a spherical type, a cylindrical type, an elliptical type, an irregular type, or the like.
According to a specific embodiment, the micro-suppository is in the form of a tablet or cylinder, and the micro-suppository has dimensions comprising: the length is 1mm-5mm, and the diameter or width is 1mm-5 mm.
In a third aspect, the present invention provides a method of preparing a micro-suppository according to the second aspect, comprising: the composition is prepared by melting, extruding, molding and cutting the mixture of the composition of the first aspect.
Preferably, the method comprises a hot melt extrusion process.
The hot-melt extrusion process comprises the steps of mixing materials, feeding the materials into a hot-melt extruder, heating the materials in a machine barrel and under the action of strong shearing force, melting, dispersing and fully and uniformly mixing the materials, finally extruding the materials from a die head through screw extrusion, obtaining a product with a set size after extrusion, and fully ensuring that the medicine and a matrix are uniformly dispersed in the preparation process.
According to a particular embodiment, the process is carried out in a hot melt extruder.
The extrusion temperature of the hot melt extruder can be 30-100 ℃, and is selected according to the melting point of specific materials.
The inlet temperature and the outlet temperature of the hot-melt extruder are respectively and independently 20-80 ℃, and are selected according to the melting point of specific materials.
Preferably, the inlet or outlet temperature of the hot melt extruder is 15-40 ℃ lower, preferably 20-25 ℃ lower, than the extrusion temperature.
Preferably, the extrusion speed of the hot melt extruder is 50-1000 rpm.
The invention provides a capsule preparation for cavity administration, which is characterized by comprising a capsule shell and a micro suppository wrapped in the capsule shell, wherein the micro suppository is the micro suppository of the second aspect and/or the micro suppository prepared by the method of the third aspect.
The micro suppository is wrapped in the capsule shell and placed in the cavity, the capsule shell can be rapidly softened to expose the micro suppository, obvious foreign body sensation cannot exist after administration due to the small size of the micro suppository, the oil-based matrix contained in the micro suppository is reduced, the contact area with the cavity is large, and the phenomenon of leakage cannot be caused after administration. In addition, the number of the micro-suppositories can be flexibly adjusted according to dosage requirements, and the micro-suppositories with different release rates can be assembled to meet the requirements of drug release. In special cases, the patient can also buy the capsule shell and the micro suppository separately for the treatment, and then the capsule shell and the micro suppository are filled automatically according to the guidance of a doctor or the charge of a medical staff, so that the dosage can be adjusted in time flexibly according to the treatment requirement.
Preferably, the material of the capsule shell is, for example, gelatin and the like. The capsule shell is commercially available.
Preferably, the capsule preparation for cavity administration is a capsule preparation for anal administration, and the size is determined according to the requirement, for example, a capsule shell of No. 00, No. 0 or No. 1 is used.
Through the technical scheme, compared with the prior art, the invention at least has the following advantages:
1) the micro-suppository can not cause foreign body sensation after administration and can not generate the situation of leakage of liquid medicine;
2) the suppository is prepared by adopting a hot-melt extrusion process for the first time, the production process is simple, the medicine can be uniformly mixed, and the suppository with high drug-loading rate can be prepared;
3) the combination mode is flexible, and the suppositories with different administration dosages and different drug release rates can be obtained;
4) a very high drug loading can be achieved.
The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.
Detailed Description
The present invention will be described in detail below by way of examples. The described embodiments of the invention are only some, but not all embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It is understood that the agents of the present invention do not require a choice of drug, and the following examples and comparative examples are given by way of illustration only of mesalamine.
Example 1
(one) preparing a composition
(1) Drug group: mesalazine, 100 parts by weight;
(2) the matrix group, which is 100 parts by weight in total, comprises:
oil-soluble base: cocoa butter, 50 parts by weight;
water-soluble base: 50 parts of gelatin;
(II) preparing micro suppository and anus administration capsule
Mixing the components of the composition, placing the mixture in a hot-melt extruder, setting the extrusion temperature to be 42 +/-3 ℃, setting the inlet and outlet temperatures to be 28 +/-2 ℃ respectively, extruding at the speed of 80rpm, collecting the extrudate, cooling and cutting the extrudate into micro-tablets with the length of 3mm, namely the micro-suppository.
And filling the micro suppository by using a No. 0 capsule shell to obtain the anus administration capsule product, wherein the medicine content reaches 50 percent by weight.
During use, the tablet is found to be small and the arrangement mode has strong plasticity because the tablet is exposed after the capsule shell is softened, and the foreign body sensation generated when the conventional suppository is used is almost not generated.
Example 2
(one) preparing a composition
(1) Drug group: mesalazine, 100 parts by weight;
(2) a matrix group, which is 150 parts by weight in total and comprises:
oil-soluble base: 50 parts by weight of semisynthetic fatty glyceride;
water-soluble base: 110 parts of polyethylene glycol;
(II) preparing a micro suppository by referring to the method of example 1.
The obtained capsule for anus administration contains 40 wt%.
Example 3
(one) preparing a composition
(1) Drug group: mesalazine, 100 parts by weight;
(2) the matrix group, which is 200 parts by weight in total, comprises:
oil-soluble base: 58 parts of semisynthetic fatty glyceride;
water-soluble base: 142 parts of polyethylene glycol;
(II) preparing a micro suppository by referring to the method of example 1.
The capsule for anus administration is obtained, wherein the medicine content reaches 33 weight percent.
EXAMPLE 4 group
The present set of examples is used to illustrate the effect of the drug and matrix composition ratios.
This set of examples was performed as in example 1, except that the ratio of the drug group and the matrix group was changed (keeping the internal ratio constant), specifically:
example 4a
100 parts of a medicine group and 50 parts of a matrix group; preparing a micro-suppository according to the method of example 1; finally obtaining the anus administration capsule, wherein the medicine content reaches 67 percent by weight;
example 4b
100 parts of a medicine group and 300 parts of a matrix group; preparing a micro-suppository according to the method of example 1; finally obtaining the anus administration capsule, wherein the medicine content reaches 25 weight percent.
Example 5
The purpose of this example is to formulate a 60% by weight anal delivery capsule.
The obtaining method comprises the following steps: the micro-suppository with drug loading of 50 wt% obtained in example 1 and the micro-suppository with drug loading of 67 wt% obtained in example 4a were mixed at a weight ratio of 40:60 to obtain an anal administration capsule with drug loading of 60%.
Similarly, in order to achieve different blood concentrations, the anus drug delivery capsule with specific drug loading can be obtained by adjusting the proportion of a plurality of micro-suppositories with different drug loading rates so as to meet the requirements of the blood concentrations, and the preparation is convenient and flexible;
similarly, by adjusting the micro-suppositories of several different base formulations in order to achieve a specific drug release rate, the drug release rate can be flexibly adjusted to patients with different tolerability, better meeting clinical needs; generally, as the proportion of the oil-soluble matrix increases, the release rate increases; the release rate is reduced when the proportion of the water-soluble matrix is increased.
Comparative example 1
The procedure was followed for the composition and method of example 1 except that the matrix group was a single-component oil-soluble matrix, namely, 100 parts by weight of semisynthetic fatty acid glycerides. Finally obtaining the anus drug delivery capsule product.
During use, it was found that the formulation melted too quickly, resulting in leakage of the drug.
Comparative example 2
The procedure is followed for the composition and method of example 1 except that the matrix group is a single component water soluble matrix, i.e., 100 parts by weight polyethylene glycol. Finally obtaining the anus drug delivery capsule product.
During use, the preparation is found to melt too slowly, so that the drug is released too slowly and normal excretion of patients is influenced.
The preferred embodiments of the present invention have been described above in detail, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, many simple modifications can be made to the technical solution of the invention, including combinations of various technical features in any other suitable way, and these simple modifications and combinations should also be regarded as the disclosure of the invention, and all fall within the scope of the invention.

Claims (10)

1. A composition for a micro-suppository, wherein the composition comprises a base group and optionally a drug group; wherein the matrix group comprises an oil-soluble matrix and a water-soluble matrix, and the weight ratio of the oil-soluble matrix to the water-soluble matrix is 1: (0.2-5).
2. The composition of claim 1, wherein the weight ratio of the oil-soluble matrix to the water-soluble matrix is 1: (0.5-3);
preferably, the oil-soluble base is selected from one or more of cocoa butter, semisynthetic fatty acid glycerides, lanolin, allspice butter, and derivatives thereof;
preferably, the water soluble matrix is selected from one or more of gelatin, polyethylene glycol and derivatives thereof.
3. The composition of claim 1 or 2, wherein the matrix set comprises one or more of the following combinations: cocoa butter and gelatin in a weight ratio of 1: (0.8-2), semisynthetic fatty acid and polyethylene glycol in a weight ratio of 1: (2-2.5);
preferably, the matrix group is contained in an amount of 30 to 500 parts by weight, preferably 50 to 250 parts by weight, with respect to 100 parts by weight of the drug group.
4. The composition of claim 1, wherein the composition further comprises an absorption interfering group comprising an absorption enhancer and/or an absorption blocker;
preferably, the absorption interfering group is contained in an amount of 10 to 40 parts by weight, preferably 20 to 30 parts by weight, with respect to 100 parts by weight of the drug group.
5. The composition of claim 4, wherein the absorption enhancer is selected from one or more of laurocapram, salicylic acid, sodium bicarbonate, urea, β 2 cyclodextrin, N2 acylamino acid, adipic acid, and derivatives thereof;
preferably, the absorption retardant is selected from one or more of natural soybean phospholipids, hydrogenated soybean phospholipids, alginic acid, stearic acid, beeswax and hydroxypropylmethyl cellulose.
6. The composition according to claim 1, wherein the composition further comprises a surfactant, and the surfactant is contained in an amount of 5 to 50 parts by weight, relative to 100 parts by weight of the drug group;
preferably, the composition further comprises an auxiliary material, wherein the auxiliary material is selected from one or more of a diluent, a lubricant and a bacteriostatic agent; the content of the auxiliary materials is 5-100 parts by weight relative to 100 parts by weight of the medicine group.
7. A micro-suppository comprising or prepared from a composition according to any one of claims 1 to 6;
preferably, the dimensions of the micro-suppository include: the length is 1mm-5mm, and the diameter or width is 1mm-5 mm.
8. A method of making a micro-suppository as claimed in claim 7, comprising: the composition of any one of claims 1-6, wherein the composition is obtained by melting, extruding, molding, and cutting a mixture.
9. The method of claim 8, wherein the steps of melting and extruding are performed in a hot melt extruder.
10. A capsule preparation for oral administration, which comprises a capsule shell and a micro-suppository encapsulated inside the capsule shell, wherein the micro-suppository is the micro-suppository of claim 7 and/or the micro-suppository prepared by the method of claim 8 or 9;
preferably, the capsule preparation for cavity and tract administration is a capsule preparation for anal administration.
CN202111257827.7A 2021-10-27 2021-10-27 Micro suppository and composition and preparation method thereof Pending CN113813223A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103720638A (en) * 2013-12-31 2014-04-16 哈尔滨欧替药业有限公司 Fenticonazole nitrate vaginal expansive suppository and preparation method and detection method thereof
CN104147604A (en) * 2014-08-27 2014-11-19 山西同达药业有限公司 Suppository substrate and preparation method thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103720638A (en) * 2013-12-31 2014-04-16 哈尔滨欧替药业有限公司 Fenticonazole nitrate vaginal expansive suppository and preparation method and detection method thereof
CN104147604A (en) * 2014-08-27 2014-11-19 山西同达药业有限公司 Suppository substrate and preparation method thereof

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