CN115531493B - Compound preparation and preparation method thereof - Google Patents

Compound preparation and preparation method thereof Download PDF

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Publication number
CN115531493B
CN115531493B CN202211207285.7A CN202211207285A CN115531493B CN 115531493 B CN115531493 B CN 115531493B CN 202211207285 A CN202211207285 A CN 202211207285A CN 115531493 B CN115531493 B CN 115531493B
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yinqiao
mixing
vitamin
preparation
compound
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CN115531493A (en
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管悦琴
孙盛华
王秀兰
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Jiuhua Huayuan Pharmaceutical Guilin Co ltd
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Jiuhua Huayuan Pharmaceutical Guilin Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/35—Caprifoliaceae (Honeysuckle family)
    • A61K36/355—Lonicera (honeysuckle)
    • 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 
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    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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    • A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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Abstract

The application relates to the technical field of pharmaceutical preparations, in particular to a compound preparation and a preparation method thereof. The compound preparation is a compound vitamin C-fimbriae forsythia oral cavity rapid disintegrating tablet, and the raw materials of the functional components of the compound preparation consist of effective doses of traditional Chinese medicine components and western medicine components; the Chinese medicinal materials are selected from flos Lonicerae, fructus forsythiae, herba Schizonepetae, fructus Arctii, folium Bambusae, semen Sojae Preparatum, radix Platycodi, glycyrrhrizae radix, rhizoma Phragmitis and peppermint oil; the western medicine component is selected from ibuprofen, desloratadine and vitamin C; the auxiliary materials of the compound preparation are selected from cyclodextrin materials, adhesives, diluents, disintegrants, sweeteners, lubricants, coating agents, plasticizers and essence. Compared with the existing vitamin C Yinqiao tablet, the compound preparation of the application not only has greatly reduced adverse reaction, but also has superior quality level, remarkably shortened onset time and high bioavailability, and can provide a pharmaceutical preparation with higher quality controllability, effectiveness and better safety for clinic.

Description

Compound preparation and preparation method thereof
Technical Field
The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a compound preparation and a preparation method thereof.
Background
Wind-heat colds (Common Cold with Wind-heat syncdrome) are mainly caused by pathogenic wind-heat invading the exterior and lung qi failing to control. The main symptoms of wind-heat type common cold include slight aversion to wind, severe fever, night sweat, headache, cough, sore throat, sticky or yellow phlegm, thirst, nasal obstruction, red edge of the tip of the tongue, thin tongue fur Bai Weihuang, etc. The spring is the frequent season of wind-heat type common cold, mainly caused by exogenous wind-heat. In the theory of disease sources and wind-heat, it is recorded that wind-heat is caused by wind-heat and qi enters the lung from the fur. The lung is the upper cover of the five zang organs, and the skin and hair of the body are damaged by wind-heat, which is the case when the skin and skin striae are deficient. It can cause aversion to wind and chill, target desquamation, nasal discharge and saliva, so it is indicated for wind-heat with pungent and cool feeling. The prescription is mulberry leaf and chrysanthemum drink, yinqiao powder, shangqing powder, jieqiao decoction, juhua powder and the like. If the patient is not healed for a long time, the patient needs to be deficient and must not be evacuated. For yang deficiency, radix Ginseng and rhizoma Atractylodis should be added, and for yin deficiency, radix rehmanniae, fructus Schisandrae chinensis, radix Ophiopogonis, and radix Paeoniae alba should be added.
The vitamin C Yinqiao tablet is a compound preparation of traditional Chinese medicine which is prepared from Yinqiao powder and is widely used for treating wind-heat type common cold for a long time. The traditional Chinese medicine part of the vitamin C Yinqiao tablet is developed from the traditional Chinese medicine "Yinqiao powder", and has been clinically used for decades. The Chinese medicine portion of the vitamin C Yinqiao tablet comprises 10 Chinese medicines of honeysuckle, weeping forsythiae capsule, fineleaf schizonepeta herb, fermented soybean and the like, and is mainly used for treating wind-heat type common cold. The western medicine part comprises chlorpheniramine maleate (i.e. chlorphenamine), acetaminophen (i.e. paracetamol) and vitamin C. Chlorpheniramine maleate and acetaminophen are common ingredients of many cold drugs. The former can relieve symptoms of lacrimation, sneeze, nasal obstruction and nasal discharge caused by common cold; the latter has antipyretic and analgesic effects, and can be used for relieving fever, muscular soreness and arthralgia caused by common cold; the vitamin C is matched, so that the body resistance can be enhanced, and the curative effect is better. The vitamin C Yinqiao tablet is a Chinese-western combined preparation which is added with chlorphenamine, paracetamol and vitamin C on the basis of Yinqiao powder, has obvious curative effect and stable and safe quality.
However, vitamin C yinqiao tablets also have some adverse reactions/events clinically. The vitamin C Yinqiao tablet is a Chinese and western medicine compound preparation prepared from 13 medicines, wherein the adverse reaction of acetaminophen contained in the tablet is mainly represented by rash, urticaria, drug fever, liver and kidney function damage, serious anaphylactic reaction and the like, and the adverse reaction of chlorpheniramine maleate contained in the tablet is mainly represented by drowsiness, weakness, somnolence, dry mouth, sore throat, palpitation and the like. At present, analysis of the national center database vitamin C Yinqiao tablet case suggests that the safety problem of the product has certain relevance with the related components contained in the product. Therefore, how to make best use of the benefits and keep short can not only exert the exact curative effect of the vitamin C Yinqiao tablet in clinical use, but also reduce, reduce or even avoid various adverse reactions brought by the vitamin C Yinqiao tablet, and improve the benefit risk ratio of the product, thus being the main problem to be solved at present.
Disclosure of Invention
The purpose of the application is to provide a compound preparation and a preparation method thereof, and aims to solve the technical problem of how to reduce adverse reactions of vitamin C Yinqiao tablet preparation.
In order to achieve the purposes of the application, the technical scheme adopted by the application is as follows:
in a first aspect, the application provides a compound preparation, wherein the compound preparation is a compound vitamin C, fendi, yinqiao oral cavity rapidly disintegrating tablet, and the raw materials of the functional components of the compound preparation comprise effective doses of traditional Chinese medicine components and western medicine components;
The Chinese medicinal materials are selected from flos Lonicerae, fructus forsythiae, herba Schizonepetae, fructus Arctii, folium Bambusae, semen Sojae Preparatum, radix Platycodi, glycyrrhrizae radix, rhizoma Phragmitis and peppermint oil;
the western medicine component is selected from ibuprofen, desloratadine and vitamin C;
the auxiliary materials of the compound preparation are selected from cyclodextrin materials, adhesives, diluents, disintegrants, sweeteners, lubricants, coating agents, plasticizers and essence.
In a second aspect, the present application provides a method for preparing a compound preparation, including the following steps:
providing raw materials and auxiliary materials of functional components of the compound preparation;
mixing flos Lonicerae, fructus forsythiae and herba Schizonepetae, and extracting to obtain volatile oil and residue;
mixing the residue with folium Bambusae, semen Sojae Preparatum, radix Platycodi, glycyrrhrizae radix and rhizoma Phragmitis, and extracting to obtain first filtrate; extracting burdock to obtain a second filtrate; mixing the first filtrate and the second filtrate, concentrating and drying to obtain dry paste powder;
mixing the Yinqiao volatile oil with peppermint oil and cyclodextrin materials to obtain a Yinqiao peppermint volatile oil cyclodextrin inclusion compound;
mixing, coating and granulating a plasticizer, a coating agent, dry paste powder and part of adhesive to obtain coated particles of the fructus forsythiae;
mixing ibuprofen, desloratadine, vitamin C, a diluent, a disintegrating agent, a sweetener, a lubricant, essence and the rest binder with the Yinqiao menthol volatile oil cyclodextrin inclusion compound and the Yinqiao coated particles, and directly tabletting to obtain the compound preparation.
The compound preparation provided by the first aspect of the application is a compound vitamin C fiveland Yinqiao oral cavity rapid disintegrating tablet, which is characterized in that acetaminophen and chlorpheniramine maleate which are easy to cause adverse reactions are replaced by ibuprofen and desloratadine, and the original common tablet is replaced by the oral cavity rapid disintegrating tablet, so that on the premise of continuously keeping the original clinical use advantages, part of absorption parts of the compound preparation are changed from gastrointestinal tract absorption to oral mucosa absorption, and part of absorption parts are still kept, and on the basis of the compound preparation, the onset time of the medicine can be shortened, and the bioavailability of the medicine is improved. Therefore, compared with the existing vitamin C Yinqiao tablet, the compound preparation of the application not only has greatly reduced adverse reaction, but also has superior quality level, obviously shortened onset time and high bioavailability, and can provide a pharmaceutical preparation with higher quality controllability, effectiveness and better safety for clinic.
According to the preparation method of the compound preparation provided by the second aspect of the application, acetaminophen and chlorpheniramine maleate in active ingredient raw materials of the vitamin C Yinqiao tablet are replaced by ibuprofen and desloratadine, auxiliary materials for preparing the oral rapid disintegrating tablet are used, and the compound vitamin C and the vitamin C and chlorpheniramine maleate oral rapid disintegrating tablet is obtained through specific steps. Compared with the existing tablet prepared by vitamin C Yinqiao tablet technology, the preparation method not only ensures that the dosage form has superior quality level, obviously shortened onset time and high bioavailability, but also has greatly reduced adverse reaction, and can provide a pharmaceutical preparation with higher quality controllability, effectiveness and better safety for clinic.
Detailed Description
In order to make the technical problems, technical schemes and beneficial effects to be solved by the present application more clear, the present application is further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the present application.
In this application, the term "and/or" describes an association relationship of an association object, which means that there may be three relationships, for example, a and/or B may mean: a alone, a and B together, and B alone. Wherein A, B may be singular or plural. The character "/" generally indicates that the context-dependent object is an "or" relationship.
In the present application, "at least one" means one or more, and "a plurality" means two or more. "at least one of" or the like means any combination of these items, including any combination of single item(s) or plural items(s).
It should be understood that, in various embodiments of the present application, the sequence number of each process does not mean that the sequence of execution is sequential, and some or all of the steps may be executed in parallel or sequentially, where the execution sequence of each process should be determined by its functions and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.
The terminology used in the embodiments of the application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in this application and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.
The weights of the relevant components mentioned in the embodiments of the present application may refer not only to specific contents of the components, but also to the proportional relationship between the weights of the components, and thus, any ratio of the contents of the relevant components according to the embodiments of the present application may be enlarged or reduced within the scope disclosed in the embodiments of the present application. Specifically, the mass described in the specification of the examples of the present application may be a mass unit known in the chemical industry such as μ g, mg, g, kg.
The terms "first" and "second" are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated for distinguishing between objects such as substances from each other. For example, a first XX may also be referred to as a second XX, and similarly, a second XX may also be referred to as a first XX, without departing from the scope of embodiments of the present application. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include one or more such feature.
The first aspect of the embodiment of the application provides a compound preparation, wherein the compound preparation is a compound vitamin C, fendi, yinqiao oral cavity rapidly disintegrating tablet, and the raw materials of the functional components of the compound preparation comprise effective doses of traditional Chinese medicine components and western medicine components;
the Chinese medicinal materials are selected from flos Lonicerae, fructus forsythiae, herba Schizonepetae, fructus Arctii, folium Bambusae, semen Sojae Preparatum, radix Platycodi, glycyrrhrizae radix, rhizoma Phragmitis and peppermint oil;
the western medicine component is selected from ibuprofen, desloratadine and vitamin C;
the auxiliary materials of the compound preparation are selected from cyclodextrin materials, adhesives, diluents, disintegrants, sweeteners, lubricants, coating agents, plasticizers and essence.
The compound preparation provided by the embodiment of the application is a compound vitamin C fiveland Yinqiao oral cavity rapid disintegrating tablet, which is characterized in that acetaminophen and chlorpheniramine maleate which are easy to cause adverse reactions are replaced by ibuprofen and desloratadine, and the original common tablet is replaced by the oral cavity rapid disintegrating tablet, so that on the premise of continuously keeping the original clinical use advantages, part of absorption parts of the compound preparation are changed from gastrointestinal tract absorption to oral mucosa absorption, and part of the compound preparation still keeps the original absorption parts, and on the basis of the compound preparation, the onset time of the medicine can be shortened, and the bioavailability of the medicine is improved. Therefore, compared with the existing vitamin C Yinqiao tablet, the compound preparation of the embodiment of the application not only has a great reduction in adverse reaction, but also has superior quality level, remarkably shortened onset time and high bioavailability, and can provide a pharmaceutical preparation with higher quality controllability, effectiveness and better safety for clinic.
Compared with the effect of acetaminophen in the treatment of infantile infectious fever, ibuprofen has better effect, faster onset of action and higher safety. Desloratadine has good curative effects on chronic idiopathic urticaria, seasonal allergic dermatitis (including nasal congestion) and perennial allergic rhinitis, has little adverse reaction and no toxic effect on heart, and can be safely taken together with some medicines for inhibiting cytochrome P450. Therefore, the paracetamol and chlorpheniramine maleate which easily cause main adverse reactions are replaced by ibuprofen and desloratadine, the original clinical use advantages of the product are kept and developed, the original common tablet is changed into the orally rapidly disintegrating tablet, the adverse reactions can be greatly reduced, and the tablet has the advantages of excellent quality level, remarkably shortened onset time and high bioavailability.
In one embodiment, the compound preparation comprises the following functional component raw materials of honeysuckle, weeping forsythia, schizonepeta, burdock, lophatherum gracile, fermented soybean, platycodon grandiflorum, liquorice, reed rhizome, peppermint oil, ibuprofen, desloratadine and vitamin C in a weight ratio of 170-190: 170-190: 70-75: 100-115: 70-75: 85-95: 100-115: 85-95: 100-115: 1.0 to 1.1: 100-110: 0.5 to 0.7: 48-52. Further, the weight ratio of honeysuckle, weeping forsythiae capsule, fineleaf schizonepeta herb, great burdock achene, lophatherum gracile, fermented soybean, platycodon grandiflorum, liquorice, reed rhizome, peppermint oil, ibuprofen, desloratadine and vitamin C is 180:180:72:108:72:90:108:90:108:1.08:105:0.6:49.5. the 13 medicines are prepared into a compound preparation of Chinese and western medicines according to the proportion, and the compound preparation has good curative effect.
In one embodiment, the auxiliary materials of the compound preparation comprise cyclodextrin materials, adhesive, diluent, disintegrating agent, sweetener, lubricant, coating agent, plasticizer and essence in a weight ratio of 7.2-36: 10 to 52:39 to 198: 6-33: 1 to 5:1 to 6:20 to 105: 5-25: 0.3 to 1.5. The auxiliary materials with the mass ratio and the 13 medicines are compounded to prepare the compound vitamin C, fendi and Yinqiao oral rapid disintegrating tablet with low adverse reaction and excellent quality level and bioavailability.
In one embodiment, the cyclodextrin-based material is selected from dimethyl- β -cyclodextrin or β -cyclodextrin derivatives, wherein the β -cyclodextrin derivatives may be alkylated derivatives, acyl derivatives, N-functional group containing derivatives, halogenated derivatives, 6-deoxy derivatives, sulfur-containing derivatives, silyl derivatives, blocked derivatives, carboxyl-containing derivatives, carbonate and carbamate glucosyl-cyclodextrin derivatives, cyclodextrin derivatives altering monosaccharide units, and the like. The cyclodextrin material is used for clathrating the fructus forsythiae volatile oil and the peppermint oil. In a preferred embodiment, the cyclodextrin material is selected from dimethyl-beta-cyclodextrin, and the solvent used in the preparation can be water or 20% -80% ethanol; the precipitation temperature of the cyclodextrin material is 2-6 ℃.
In one embodiment, the binder is selected from at least one of povidone, low substituted hydroxypropyl cellulose, pregelatinized starch, alginic acid, lactose, chitosan, hypromellose, cellulose acetate, ethylcellulose, methylethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, carboxymethyl ethyl cellulose, cellulose acetate, cellulose propionate, cellulose butyrate, cellulose acetate butyrate, hypromellose phthalate, hypromellose acetate succinate, hydroxypropyl methylcellulose acetate trimellitate, ethylhydroxyethyl cellulose, vinyl acetate povidone polymer matrix, sodium polyacrylate, and polyoxyethylene (160) polyoxypropylene (30) glycol, polyethylene oxide, pullulan, polyvinyl alcohol, polyvinyl acetate, glyceryl fatty acid esters, polyacrylamide, polyacrylic acid, copolymers of ethyl acrylic acid or methacrylic acid. Wherein, the povidone in the adhesive can be povidone K30, and the low-substituted hydroxypropyl cellulose can be low-substituted hydroxypropyl cellulose with the substitution degree of 5-16%, such as low-substituted hydroxypropyl cellulose L-11; in a preferred embodiment, the binder is low-substituted hydroxypropyl cellulose L11 and povidone K30 according to the mass ratio of 10-50: 0.5 to 2.5, and the two adhesives are mixed and matched, thereby having better bonding effect. Povidone K30 was formulated with 60% ethanol solution.
In one embodiment, the diluent is selected from at least one of dextrates, low substituted hydroxypropylcellulose, sorbitol, mannitol, chitosan, pregelatinized starch, lactose, sucrose, hydroxypropylcellulose, and hypromellose. In a preferred embodiment, the diluent comprises 13 to 66 mass percent of glucose bond, mannitol and sorbitol: 13 to 66: 13-66.
In one embodiment, the disintegrant is selected from at least one of sodium carboxymethyl starch, low substituted hydroxypropyl cellulose, povidone, alginic acid, calcium carboxymethyl cellulose, colloidal silicon dioxide, guar gum, chitosan, sodium carboxymethyl cellulose, croscarmellose sodium, hydroxypropyl methylcellulose, hydroxypropyl cellulose, microcrystalline cellulose, powdered cellulose, pregelatinized starch, and potassium polacrilin; in a preferred embodiment, the disintegrant is selected from sodium carboxymethyl starch.
In one embodiment, the sweetener is selected from at least one of sucralose, mannitol, sorbitol, aspartame, acesulfame potassium, alitame, fructose, mannitol, maltose, and sodium cyclamate; in a preferred embodiment, the sweetener is selected from sucralose.
In one embodiment, the lubricant is selected from at least one of magnesium stearate, sodium stearyl fumarate, sodium stearate, stearic acid, glyceryl palmitostearate, poloxamer, stearyl hexadecanol, and zinc stearate; magnesium stearate is preferred.
In one embodiment, the coating agent is selected from at least one of eudragit, cetyl alcohol, chitosan, cellulose acetate, ethylcellulose, hydroxyethyl cellulose, hydroxyethyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate, poly (meth) acrylic resin, polyvinyl acetate phthalate, polyvinyl alcohol, maltitol, methylcellulose, and xylitol; for example, the coating agent is preferably Uttky E12.5 (i.e., a coating liquid having a coating agent Uttky E solids content of 12.5%).
In one embodiment, the plasticizer is selected from at least one of diethyl phthalate, triethyl citrate, tributyl citrate, dimethyl phthalate, dipropyl phthalate, dibutyl phthalate, chitosan, paraffin, corn oil, refined coconut oil, monoacetin, triacetin, glycerol, polyethylene glycol, triethyl phthalate, tributyl phthalate, dibutyl sebacate, diethyl sebacate, glyceryl stearate, diethyl succinate, propylene glycol, castor oil, tributyl acetylcitrate, triethyl acetylcitrate, and glyceryl triacetate; the plasticizer is preferably diethyl phthalate.
In one embodiment, the flavour is selected from orange flavour.
A second aspect of the embodiments of the present application provides a method for preparing the above compound preparation, including the following steps:
s01: providing the raw materials and auxiliary materials of the functional components of the compound preparation;
s02: mixing flos Lonicerae, fructus forsythiae and herba Schizonepetae, and extracting to obtain volatile oil and residue;
s03: mixing the residue with folium Bambusae, semen Sojae Preparatum, radix Platycodi, glycyrrhrizae radix and rhizoma Phragmitis, and extracting to obtain first filtrate; extracting burdock to obtain a second filtrate; mixing the first filtrate and the second filtrate, concentrating and drying to obtain dry paste powder;
s04: mixing the Yinqiao volatile oil with peppermint oil and cyclodextrin materials to obtain a Yinqiao peppermint volatile oil cyclodextrin inclusion compound;
s05: mixing, coating and granulating a plasticizer, a coating agent, dry paste powder and part of adhesive to obtain coated particles of the fructus forsythiae;
s06: mixing ibuprofen, desloratadine, vitamin C, a diluent, a disintegrating agent, a sweetener, a lubricant, essence and the rest binder with the Yinqiao menthol volatile oil cyclodextrin inclusion compound and the Yinqiao coated particles, and directly tabletting to obtain the compound preparation.
According to the preparation method of the compound preparation provided by the embodiment of the application, acetaminophen and chlorpheniramine maleate in active ingredient raw materials of the vitamin C Yinqiao tablet are replaced by ibuprofen and desloratadine, auxiliary materials for preparing the oral rapid disintegrating tablet are used, and the compound vitamin C and the vitamin C and chlorpheniramine maleate oral rapid disintegrating tablet is obtained through specific steps. Compared with the existing tablet prepared by vitamin C Yinqiao tablet technology, the preparation method not only ensures that the dosage form has superior quality level, obviously shortened onset time and high bioavailability, but also has greatly reduced adverse reaction, and can provide a pharmaceutical preparation with higher quality controllability, effectiveness and better safety for clinic.
In step S01, the kinds and proportions of the raw materials and auxiliary materials for the functional components are described in detail above.
In step S02, the extraction step of the Yinqiao volatile oil is performed. Specifically, the method comprises the following steps: placing the crushed fructus forsythiae and herba Schizonepetae coarse powder and flos Lonicerae in an extractor, introducing steam under vacuum degree of-0.04 MPa to-0.09 MPa, heating and extracting, and collecting fructus forsythiae volatile oil.
In the step S03, a dry paste powder preparation step of the traditional Chinese medicine is adopted. Specifically, the method comprises the following steps: taking out the residue after extracting the Yinqiao volatile oil, putting the residue, the lophatherum gracile, the fermented soya beans, the reed rhizome, the platycodon grandiflorum and the liquorice together into an extractor, adding water for soaking for 12 hours, then decompressing (-0.04 MPa to-0.09 MPa), heating for 70-80 ℃ for reflux extraction for two times, and combining the filtrates to obtain a first filtrate; adding 60% ethanol with the amount of 6 times of the prescription into an extractor, immersing for 12 hours, heating for 60-70 ℃ and decompressing (-0.04 MPa to-0.09 MPa) for reflux extraction for two times, combining the filtrates, decompressing (-0.04 MPa to-0.09 MPa) for recovering the ethanol until the relative density is 1.05-1.10 (70 ℃), pumping the liquid medicine into a jacketed kettle, adding paraffin while the liquid medicine is hot for full dissolution, introducing cooling water into the jacket of the jacketed kettle, cooling the concentrated solution until the paraffin floats on the liquid level, and removing the paraffin layer to obtain the final filtrate, namely the second filtrate. Mixing the first filtrate and the second filtrate, concentrating to obtain a proper amount of clear paste with the relative density of 1.05-1.10 (60 ℃); then spray drying and pulverizing into 120 mesh fine powder, namely the dry paste powder.
In the step S04, the preparation step of the forsythia peppermint volatile oil cyclodextrin inclusion compound is adopted. May include: grinding cyclodextrin in ethanol solution to obtain cyclodextrin saturated ethanol solution; mixing and grinding the cyclodextrin saturated ethanol solution, the forsythia volatile oil and the peppermint oil, refrigerating at the temperature of 2-6 ℃ until crystallization is separated out, and carrying out suction filtration and drying to obtain the forsythia peppermint volatile oil cyclodextrin inclusion compound. The Yinqiao volatile oil and the peppermint oil are included by cyclodextrin, so that the process complexity of adding the Yinqiao volatile oil and the peppermint oil is reduced, the volatilization of the Yinqiao volatile oil and the peppermint oil can be better avoided, the loss of the Yinqiao volatile oil and the peppermint oil caused by heating and drying is avoided, and the Yinqiao volatile oil and the peppermint oil are ensured to be added into the total mixed particles.
In step S05, a step of preparing the coated particles of honeysuckle flower and forsythia is performed. May include; dispersing a plasticizer in the coating agent to obtain a granule coating agent; mixing the dry paste powder with part of the binder to prepare a soft material, sieving with a 20-mesh sieve to prepare wet particles, boiling and drying at 65-75 ℃ until the water content is 3.2-3.6%, and sieving with a 14-mesh sieve to obtain the Yinqiao particles; placing the Yinqiao granules in a coating machine, adjusting the air inlet temperature to 80-90 ℃, the rotating speed of the coating machine to 2-4 rpm/min, preheating to the air outlet temperature to 45-50 ℃, spraying the granule coating agent, gradually increasing the rotating speed to 6-9 rpm/min, increasing the air inlet quantity and the spraying flow of the coating agent, and enabling the coating agent on the surfaces of the granules to be sufficiently dried until all the granule coating agent is used up to obtain the Yinqiao coated granules. Wherein, if the adhesive is composed of low-substituted hydroxypropyl cellulose L-11 and povidone K30, the partial adhesive can be 1/3 of the low-substituted hydroxypropyl cellulose L-11 and the whole povidone K30. The remaining binder was 2/3 of the low-substituted hydroxypropylcellulose L-11.
In one embodiment, the preparation steps of the Yinqiao coated particles comprise: and uniformly dispersing the plasticizer diethyl phthalate in the coating agent Uttky E12.5 to obtain the granule coating agent. Mixing the dry paste powder with 1/3 of low-substituted hydroxypropyl cellulose L-11 uniformly, adding all povidone K30 (the concentration is 5%, the solvent is 60% ethanol solution) to prepare soft materials, sieving with a 20-mesh sieve to prepare wet particles, boiling and drying at 65-75 ℃ until the water content is 3.2% -3.6%, and sieving with a 14-mesh sieve to obtain the Yinqiao particles for standby. Placing the Yinqiao granules in a non-porous coating machine, regulating the air inlet temperature to 80-90 ℃, the rotating speed of the coating machine to 2-4 rpm/min, preheating to the air outlet temperature to 45-50 ℃, spraying the granule coating agent, controlling the spraying flow to uniformly cover the granule coating agent on the surface of the granules, gradually increasing the rotating speed to 6-9 rpm/min, increasing the air inlet quantity and the spraying flow of the granule coating agent, fully drying the granule surface until all the granule coating agent is used up, finally gradually reducing the air inlet temperature until the air outlet temperature is cooled to the room temperature (25-27 ℃), and continuously cooling the coated granules in the coating machine to the room temperature.
In the step S05, the method is a step of forming the compound vitamin C Fender Yinqiao oral cavity rapidly disintegrating tablet. Wherein, in the process of mixing ibuprofen, desloratadine, vitamin C, a diluent, a disintegrating agent, a sweetener, a lubricant, essence and the rest binder with the Yinqiao volatile oil cyclodextrin inclusion compound and the Yinqiao coated particles for wet granulation, the diluent is added by an equal progressive addition method.
In one embodiment, the wet granulating step includes: the ibuprofen, the desloratadine and the vitamin C are respectively crushed into 120-mesh fine powder. Placing the crushed desloratadine into a wet mixing granulator, sequentially adding orange essence and a sweetener sucralose, uniformly mixing, and adding a diluent (glucose-binding agent, mannitol and sorbitol) by an equal progressive method, and uniformly mixing; continuously adding ibuprofen and vitamin C fine powder, mixing, remaining adhesive low-substituted hydroxypropyl cellulose L-11, yinqiao menthol volatile oil cyclodextrin inclusion compound, yinqiao coated particles, disintegrating agent carboxymethyl starch sodium and lubricant magnesium stearate, uniformly mixing, and directly pressing into tablets to obtain the final product.
The compound vitamin C and the Yinqiao oral rapid disintegrating tablet prepared by the embodiment of the application is characterized in that acetaminophen and chlorpheniramine maleate are replaced by ibuprofen and desloratadine, and the original common tablet is changed into the oral rapid disintegrating tablet, and in the process, the stability of the vitamin C can be improved by mixing the vitamin C with the Yinqiao volatile oil cyclodextrin inclusion compound, so that the adverse reaction is greatly reduced finally, and the compound vitamin C and the Yinqiao oral rapid disintegrating tablet has superior quality level, remarkably shortened onset time and high bioavailability, and can provide a pharmaceutical preparation with higher quality controllability, effectiveness and better safety for clinic. The lower age limit of the medication can be reduced to 6 months of age in the event that sufficient cases are accumulated.
The following description is made with reference to specific embodiments.
Example 1
Preparation of composite vitamin C Fender Yinqiao orally fast disintegrating tablet
1.1 prescription raw materials prescription is given in table 1 below.
TABLE 1
1.2 preparation method
1.2.1 extracting the Yinqiao volatile oil: pulverizing fructus forsythiae and herba Schizonepetae into coarse powder; adding a barrier into an extractor, adding drinking water, enabling the water surface of the drinking water to be 10cm away from the lower surface of the barrier, spreading fructus forsythiae, coarse schizonepeta powder and honeysuckle on the barrier, closing an upper cover of the extractor, starting a vacuum pump to enable the vacuum degree in the extractor to be minus 0.04MPa to minus 0.09MPa, introducing steam to heat so that the drinking water is in a stable boiling state, opening cooling water into a condenser, controlling the water outlet temperature to be lower than 30 ℃, and extracting for 2 hours to obtain the Yinqiao volatile oil for later use.
1.2.2 preparation of dry extract powder: taking out fructus forsythiae, herba Schizonepetae and flos Lonicerae residue left after volatile oil extraction, adding into an extractor together with folium Bambusae, semen Sojae Preparatum, rhizoma Phragmitis, radix Platycodi and Glycyrrhrizae radix, adding 10 times of drinking water, soaking for 12 hr, heating under reduced pressure (-0.04 MPa to-0.09 MPa) at 70-80deg.C for two times, filtering each time for 2 hr, and mixing filtrates to obtain first filtrate. Adding 60% ethanol with the prescription amount into an extractor, soaking for 12 hours, heating for 60-70 ℃ and decompressing (-0.04 MPa to-0.09 MPa) for reflux extraction twice, filtering each time for 4 hours, combining filtrates, decompressing (-0.04 MPa to-0.09 MPa) and recovering ethanol until the relative density is 1.05-1.10 (70 ℃), pouring the liquid medicine into a jacketed kettle, adding paraffin while the liquid medicine is hot to fully dissolve, introducing cooling water into a jacket of the jacketed kettle, cooling the concentrated solution until the paraffin floats on the liquid surface, and removing a paraffin layer to obtain a second filtrate. Mixing the first filtrate and the second filtrate, and concentrating in a concentrator to obtain fluid extract with a proper relative density of 1.05-1.10 (60 ℃). Spray drying the fluid extract, and pulverizing into 120 mesh fine powder to obtain dry extract powder.
1.2.3 preparation of volatile oil clathrate: mixing the peppermint oil and the Yinqiao volatile oil uniformly to obtain the peppermint-Yinqiao mixed volatile oil. Placing dimethyl-beta-cyclodextrin into a ball mill, and adding 60% ethanol solution into the ball mill to obtain the saturated ethanol solution of dimethyl-beta-cyclodextrin. Adding the mixed volatile oil of peppermint and Yinqiao into a ball mill filled with a saturated ethanol solution of dimethyl-beta-cyclodextrin, continuously grinding and mixing, refrigerating for 12 hours at 2-6 ℃ until crystals are completely separated out, filtering, washing with 60% ethanol, and vacuum drying to obtain a volatile oil inclusion compound.
1.2.3 preparation of Yinqiao coated particles: and uniformly dispersing diethyl phthalate in the Uttky E12.5, and uniformly mixing to obtain the granule coating agent. Mixing the obtained dry paste powder with 10g of low-substituted hydroxypropyl cellulose L-11 uniformly, adding 5% povidone K30 solution (60% ethanol solution as solvent) to prepare soft materials, sieving with 20 mesh sieve to prepare wet particles, boiling and drying at 65-75 ℃ until the water content is 3.2% -3.6%, and sieving with 14 mesh sieve to obtain the Yinqiao particles. Placing the Yinqiao granules in a non-porous coating machine, adjusting the air inlet temperature to 80-90 ℃, the rotating speed of the coating machine to 2-4 rpm/min, preheating to the air outlet temperature to 45-50 ℃, spraying the granule coating agent, controlling the spraying flow to uniformly cover the granule coating agent on the surface of the granules, gradually increasing the rotating speed to 6-9 rpm/min, increasing the air inlet quantity and the spraying flow to fully dry the granule coating agent on the surface of the granules until all the granule coating agent is used up, gradually reducing the air inlet temperature until the air outlet temperature is cooled to room temperature, and continuously cooling the coated granules in the coating machine to the room temperature to obtain the Yinqiao coated granules.
1.2.4 preparation of Compound vitamin C Fendi Yinqiao oral rapidly disintegrating tablet: the ibuprofen, the desloratadine and the vitamin C are respectively crushed into 120-mesh fine powder. Placing the crushed desloratadine into a wet mixing granulator, sequentially adding orange essence and sucralose, uniformly mixing, adding a dextrant by an equal progressive method, uniformly mixing, continuously adding ibuprofen, vitamin C fine powder, mannitol, sorbitol, the rest 20g of low-substituted hydroxypropyl cellulose L-11, mint and Yinqiao mixed volatile oil cyclodextrin inclusion compound, yinqiao coated particles, carboxymethyl starch sodium and magnesium stearate, uniformly mixing, and directly pressing into tablets to obtain the compound vitamin C and Yinqiao orally rapid disintegrating tablets.
Example 2
The preparation of the compound vitamin C fendi Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 40g of mannitol, 40g of glucose bond, 40g of sorbitol, 6g of carboxymethyl starch sodium and other components and processes in the prescription are the same as those in the embodiment 1.
Example 3
The preparation of the compound vitamin C fendi Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 48g of mannitol, 12g of glucose-bonded agent and 48g of sorbitol are adopted in the prescription, and other components and processes are the same as the embodiment 1.
EXAMPLE 4
The preparation of the compound vitamin C fendi Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 48g of mannitol, 48g of glucose-bonded agent and 12g of sorbitol in the prescription, and other components and processes are the same as the embodiment 1.
EXAMPLE 5
The preparation of the compound vitamin C fendi Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 12g of mannitol, 48g of glucose-bonded agent and 48g of sorbitol in the prescription, and other components and processes are the same as the embodiment 1.
EXAMPLE 6
The preparation of the composite vitamin C fenldi and Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 42.6g of mannitol, 42.8g of glucose bond, 42.6g of sorbitol, 10g of low-substituted hydroxypropyl cellulose (which is fully added in the preparation of the Yinqiao coated particles) and other components and processes are the same as the embodiment 1.
EXAMPLE 7
The preparation of the compound vitamin C fendi Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 40.8g of mannitol, 40.8g of glucose-bonded agent, 40.8g of sorbitol and 7.2g of dimethyl-beta-cyclodextrin in the prescription, and other components and processes are the same as the embodiment 1.
Example 8
The preparation of the compound vitamin C Fender Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 46g of mannitol, 46g of glucose bond, 46g of sorbitol, 30g of Utility (E12.5) and other components and processes in the prescription are the same as those in the embodiment 1.
Example 9
The preparation of the compound vitamin C fendi Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 39g of mannitol, 39g of sorbitol, 39g of dextrates, 6g of diethyl phthalate and other components and processes in the prescription are the same as the embodiment 1.
Comparative example 1
The preparation of the compound vitamin C fendi Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 46g of mannitol, 46g of glucose bond and 46g of sorbitol are adopted in the prescription; the other components and processes were the same as in example 1 without using the addition of low-substituted hydroxypropylcellulose.
Comparative example 2
The preparation of the compound vitamin C fendi Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 42g of mannitol, 42g of glucose binder and 42g of sorbitol are adopted in the prescription; without using the sodium carboxymethyl starch, other components and processes were the same as in example 1.
Comparative example 3
The preparation of the compound vitamin C fendi Yinqiao orally disintegrating tablet is different from the embodiment 1 in that 41g of mannitol, 41g of glucose bond and 41g of sorbitol are adopted in the prescription; the other components and processes were the same as in example 1 without the addition of diethyl phthalate.
Comparative example 4
Vitamin C Yinqiao tablet with the recipe shown in Table 2 below; see under the edition 2020 of Chinese pharmacopoeia, a part of vitamin C.
TABLE 2
Preparation process
1. Extracting the fructus forsythiae volatile oil.
1.1 pulverizing fructus forsythiae and herba Schizonepetae into coarse powder.
1.2 adding a barrier into an extractor, adding drinking water to ensure that the water surface of the drinking water is 10cm away from the lower surface of the barrier, spreading fructus forsythiae, coarse powder of schizonepeta and honeysuckle on the barrier, closing an upper cover of the extractor, heating by introducing steam to ensure that the drinking water is in a stable boiling state, opening cooling water to introduce the cooling water into a condenser, heating and reflux extracting the Yinqiao volatile oil for 2 hours, and collecting the Yinqiao volatile oil for later use.
2. Extraction of medicinal materials
2.1, taking out fructus forsythiae, herba schizonepetae and honeysuckle dregs after extracting the volatile oil of the fructus forsythiae, putting the fructus forsythiae, herba schizonepetae and honeysuckle dregs, together with lophatherum gracile, fermented soybean, reed rhizome, platycodon grandiflorum and liquorice into an extractor, adding 10 times of drinking water, soaking for 12 hours, heating until an extraction solvent is in a stable boiling state, extracting under reflux for two times for 2 hours each time, filtering, and combining filtrates for later use;
2.2 placing burdock with the prescription amount in an extractor, adding 6 times of 60% ethanol, soaking for 12 hours, heating and refluxing for extraction twice, each time for 4 hours, filtering, combining the filtrates, recovering ethanol until the relative density is 1.05-1.10 (70 ℃), pumping the liquid medicine into a jacketed kettle, adding paraffin wax to fully dissolve the liquid medicine, introducing cooling water into the jacketed kettle, cooling the concentrated solution until the paraffin wax floats on the liquid surface, removing a paraffin wax layer, and reserving the filtrate.
2.3 mixing the filtrate obtained in 2.1 and 2.2, pumping into a concentrator, concentrating to a proper amount of clear paste with the relative density of 1.05-1.10 (60 ℃), spray drying, and pulverizing into fine powder to obtain spray dry paste powder A for later use.
3. Preparation of vitamin C Yinqiao tablet
3.1, taking spray dry paste powder A prepared by 2.3, adding the prescription amount of pregelatinized starch and lactose, uniformly mixing, adding a proper amount of ethanol to prepare proper soft materials, then preparing 16-mesh wet particles, boiling and drying at 65-75 ℃ until the water content is 3.5-4.3%, and sieving with a 14-mesh sieve to prepare the Yinqiao particles for later use.
Preparation of coated vitamin C-Paracetamol-chlorpheniramine maleate particles
3.2.1 dissolving chlorpheniramine maleate in 60% ethanol, adding povidone K30, and mixing to obtain 60% ethanol solution containing 5% povidone K30 of chlorpheniramine maleate.
3.2.2 taking prescription amount of acetaminophen, vitamin C and hypromellose, adding proper amount of 60% ethanol solution containing 5% povidone K30 of chlorphenamine maleate to prepare a proper soft material, sieving with 20 meshes to prepare wet granules, boiling and drying at 65-75 ℃ until the water content is 3.5% -4.3%, and sieving with 16 meshes to obtain the granules for standby.
3.2.3 taking the prescription amount of Uttky E12.5, adding the prescription amount of diethyl phthalate, mixing for 15 minutes by a high-speed homogenizer, and preparing the granule coating agent.
3.2.4 placing the vitamin C-paracetamol-chlorpheniramine maleate granules prepared by 3.2.2 into a nonporous coating machine, controlling the air inlet temperature to be 80-90 ℃, controlling the rotating speed of the coating machine to be 2-4 r/min, controlling the air outlet temperature to be 40-45 ℃, preheating the granules for 30 min, adjusting the rotating speed of the coating machine to be 7-9 r/min, spraying the granule coating agent prepared by 3.2.3, controlling the flow until the coating agent just covers the surfaces of the granules, and fully drying the granules, so as to prevent the granules from being adhered to each other due to too small granules, keeping the layers fully dried until all the coating agent covers the surfaces of the granules and fully drying the granules, and preparing the vitamin C-paracetamol-chlorpheniramine coated granules for standby.
Preparation of 3.3-D C Yinqiao tablet
Mixing vitamin C-acetaminophen-chlorpheniramine maleate coated granule and YINQIAO granule, spraying peppermint oil and YINQIAO volatile oil, moistening for 1 hr, adding glycerol monostearate and silica gel micropowder, mixing, tabletting, and coating with gastric-soluble film coating.
Effect testing
1. Content determination
1.1 vitamin C content determination
The method is measured by high performance liquid chromatography (0512) according to the four general rules of the year 2020 edition of Chinese pharmacopoeia.
1.1.1 chromatographic conditions and System applicability: the amino silane bonded silica gel is used as a filler, acetonitrile-0.01 mol/L potassium dihydrogen phosphate (pH value is regulated to 2.4 by phosphoric acid) (70:30) is used as a mobile phase, the detection wavelength is 246nm, and the theoretical plate number is not lower than 2000 calculated by vitamin C.
1.1.2 preparation of control solution: taking a proper amount of vitamin C reference substance, precisely weighing, adding 0.5% sodium bisulphite solution (pH value is adjusted to 2.4 by phosphoric acid) to prepare a solution containing 20 mug per 1 ml.
1.1.3 preparation of test solutions: taking 10 pieces of compound vitamin C buddhist nun and forsythia oral cavity rapidly disintegrating tablet, precisely weighing, grinding, taking about 1g (which is approximately equal to 100mg of vitamin C, precisely weighing, placing into a 50ml measuring flask, adding 40ml of 0.5% sodium bisulfite solution (pH value is regulated to 2.4 by phosphoric acid), performing ultrasonic treatment (power 300w and frequency 40 kHz) for 5 minutes, cooling, adding 0.5% sodium bisulfite solution to dilute to a scale, and shaking uniformly to obtain the oral cavity rapidly disintegrating tablet.
1.1.4 measuring method, respectively precisely sucking 10 μl of each of the reference substance solution and the sample solution, injecting into a liquid chromatograph, and measuring.
1.2 ibuprofen content determination
1.2.1 chromatographic conditions: diamond C18 chromatography column (5 μm,250 mm. Times.4.6 mm); 0.1% phosphoric acid solution-acetonitrile (35:65), flow rate of 1ml/min, detection wavelength of 222nm, and column temperature of room temperature; the sample loading was 10. Mu.l.
1.2.2 sample measurement: taking a sample solution under the dissolution rate, filtering, precisely measuring 10 μl of the subsequent filtrate, injecting into a liquid chromatograph, and recording a chromatogram; the control was also taken and operated in the same manner, and the peak area was calculated according to the external standard method.
1.3 desloratadine assay
The measurement is carried out by high performance liquid chromatography (China pharmacopoeia 2020 edition, four-part rule 0512).
1.3.1 chromatographic conditions and System applicability: octadecyl bonded silica gel column (5 μm,150 mm. Times.4.6 mm) is used as chromatographic column, acetonitrile-0.01 mol/L potassium dihydrogen phosphate buffer salt solution (1.37 g of potassium dihydrogen phosphate is taken and dissolved in 900ml of water), 2.5ml of triethylamine is added, pH is adjusted to 2.5 by phosphoric acid, and volume is fixed to 1000ml by water) (22:78) is used as mobile phase; the detection wavelength is 282nm, the column temperature is 35 ℃, the flow rate is 1.0ml/min, each 10 μl of the sample solution and the reference solution is precisely measured, and the sample solution and the reference solution are injected into a chromatograph to record a chromatogram; the main peak is calculated by desloratadine, the number of tower plates is not lower than 2500, and the separation degree of the main peak and the adjacent impurity peaks meets the requirement.
1.3.2 control solution: taking a proper amount of desloratadine reference substance, precisely weighing, adding a mobile phase for dissolving and diluting to obtain a solution with the concentration of 0.025mg/ml, and taking the solution as the reference substance solution.
1.3.3 sample solution: grinding compound vitamin C, fructus forsythiae, and oral rapidly disintegrating tablet 5, precisely weighing appropriate amount of powder (about equivalent to desloratadine 2 mg), placing into 50ml measuring flask, adding appropriate amount of mobile phase to dissolve, fixing volume with mobile phase, shaking, and filtering to obtain test solution.
1.3.4 assay: precisely measuring 10 μl of each of the sample solution and the reference solution, injecting into chromatograph, and recording chromatogram; and calculating according to an external standard method and peak area to obtain the product.
2. Stability determination
The stability of the raw material medicine and the preparation is measured according to the guidelines of the four-part general rule 9001 of the 2020 edition of Chinese pharmacopoeia.
Taking 10 samples of each example and comparative example, putting the samples into a measuring flask without cover, putting the measuring flask into a constant temperature and humidity box, setting the temperature to 40+/-2 ℃ and the humidity to 75+/-5%, examining for 6 months, sampling at 0 month, 1 month, 2 months, 3 months and 6 months, and measuring the vitamin C content.
3. Determination of disintegration time
3.1 in vitro disintegration time determination
Placing one tablet in each basket each time, checking according to the rule 0921 disintegration time limit check method of four portions of the edition 2020 of Chinese pharmacopoeia until the granule completely passes through the screen, recording disintegration time limit with a stopwatch, and taking average value as measurement result.
3.2 determination of the time period for oral disintegration
A single blind experiment involving six volunteers was designed to evaluate the disintegration time of orally disintegrating tablets in the oral cavity of different individuals. After rinsing with clear water, each volunteer took one orally disintegrating tablet separately and placed on the tongue, recorded the time for complete disintegration of the tablet, and calculated the mean and standard deviation.
4. Weight difference
Taking 10 tablets, precisely weighing the total weight, precisely weighing the average tablet weight, respectively, wherein the weight of each tablet is not more than 5% of the weight difference limit compared with the average tablet weight, and not more than 2 tablets exceeding the weight difference limit and not more than one time of the limit.
5. Hardness: each batch of samples was taken and its hardness was determined using each hardness score.
6. Friability degree of friability
10 pieces of the product are taken from each batch, floating dust is blown off, the weight is precisely weighed, and the weight loss is less than 1 percent according to the rule 0923 of the fourth edition of Chinese pharmacopoeia 2020.
7. Determination of Water absorption Properties
The filter paper was thoroughly wetted. The compound vitamin C Fendi Yinqiao orally disintegrating tablet is put on filter paper. After complete wetting, the weight is measured and the water absorption is calculated as follows:
W＝[(M-M 0 )/M 0 ]×100％
w% -water absorption, total tablet weight after M-water absorption, M 0 Raw sheet weights, performed three times per experiment, mean and standard deviation were calculated.
8. Comparison of bioavailability
8.1 Experimental materials
42 rabbits (2.43+/-0.21) were kg in body mass, and did not take any medicine. The 42 rabbits were randomly divided into 13 groups of 4, and 1 tablet of the oral test drug was administered in a single empty stomach. Taking 1.0ml of venous blood after 24h empty stomach and 0.25,0.5,1,1.5,2,3,4,5,7,9, 11 and 13h administration, immediately separating serum by a centrifugal machine, and storing in a refrigerator at-40 ℃ to be tested.
8.2 serum concentration determination
Taking 0.2ml of serum sample, placing the serum sample into a 1ml plastic centrifuge tube, adding 0.2ml (10 mug/ml) of indomethacin internal standard solution prepared by acetonitrile, placing the indomethacin internal standard solution into an ultrasonic cleaner for carrying out water bath ultrasonic treatment for 0.5min, centrifuging the mixture at a high speed (15000 rpm,10 min), and taking 20 mul of supernatant for sample injection. Chromatographic conditions: the analytical column was Iregullar H C18 (250 mm. Times.5 mm,10 μm) and the mobile phase was methanol: 20mmol/L potassium dihydrogen phosphate buffer (3:1), flow rate 1ml/min, detection wavelength 225nm, room temperature. The peak-out time of ibuprofen and the internal standard is 8.86 min and 6.87min respectively, and the detection limit is 2ng (S/N is more than or equal to 4). Preparing serum standard solution with the mass concentration of 0.5-32 mug/ml by the method, and carrying out linear regression on the ibuprofen to internal standard peak height ratio of (X) and the ibuprofen concentration (c);
The regression equation is x=0.04654c+0.0236 (r= 0.9986).
8.3 blood concentration determination: before administration, 3ml of blank blood is taken from the auricular vein as a control, 3ml of blood is taken after administration according to 0.5, 1, 2, 3, 4, 5, 6 and 7 hours, heparin is used for anticoagulation, the blood is gently shaken, 1ml of blood plasma containing medicine and blank blood plasma is taken after centrifugation, and the blood plasma is preserved at a low temperature for standby. Taking the above blood sample, naturally heating to room temperature, adding 10% CCl 3 Cooh1.5ml, mixing, centrifuging, collecting supernatant 1ml, operating the rest according to standard curve, substituting the measured absorbance into linear equation, and calculating blood concentration.
Measurement results
(1) Table 3 shows the results of the disintegration time, water absorption, hardness, weight difference, and friability index.
TABLE 3 Table 3
(2) The results of the vitamin C accelerated stability test (mg) are shown in Table 4.
TABLE 4 Table 4
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(3) The results of the ibuprofen and desloratadine dissolution test are shown in Table 5.
TABLE 5
(4) The results of the ibuprofen blood concentration (μg/ml) and bioavailability (AUC) (μg.h/ml) measurements are shown in Table 6.
TABLE 6
From the above data, it can be seen that: the hardness, water absorption, weight difference, friability, 0.5min and 1.0min dissolution of the compound vitamin C Fendi Yinqiao oral rapidly disintegrating tablet prepared in example 1 are superior to those of other examples and comparative examples. The quantity of the low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, mannitol, sorbitol, dextrates, diethyl phthalate and Uttky E12.5 is reduced, so that the important indexes such as the oral disintegration time limit, the dissolution rate and the bioavailability of the compound vitamin C fimbriata Yinqiao orally fast disintegrating tablet are greatly influenced by different degrees, and meanwhile, the hardness, the weight difference and the friability of the tablet are also greatly influenced. The reduction of the amount of the Uttky E12.5 obviously affects the coating thickness of the vitamin C, further affects the stability of the vitamin C, particularly the reduction of the amount of the diethyl phthalate directly affects the flexibility and the ductility of the coating film, and the stability of the vitamin C is more serious than the thickness of the coating film.
Compared with the vitamin C Yinqiao tablet in the prior art, the compound vitamin C Fendi Yinqiao oral rapid disintegrating tablet prepared by the quantity and the proportion of various auxiliary materials in the prescription is greatly reduced in adverse reaction, and the compound vitamin C Fendi Yinqiao oral rapid disintegrating tablet prepared by the method has more excellent quality level and bioavailability, can provide higher quality controllability, effectiveness and better safety for clinical use, and has better technical advantages and use value.
The foregoing description of the preferred embodiments of the present application is not intended to be limiting, but is intended to cover any and all modifications, equivalents, and alternatives falling within the spirit and principles of the present application.

Claims (6)

1. The compound preparation is characterized in that the compound preparation is a compound vitamin C, fendi, yinqiao oral cavity rapidly disintegrating tablet, and the raw materials of the functional components of the compound preparation comprise effective doses of traditional Chinese medicine components and western medicine components;
the Chinese medicinal components comprise flos Lonicerae, fructus forsythiae, herba Schizonepetae, fructus Arctii, folium Bambusae, semen Sojae Preparatum, radix Platycodi, glycyrrhrizae radix, rhizoma Phragmitis and peppermint oil; the western medicine comprises ibuprofen, desloratadine and vitamin C; the weight ratio of honeysuckle, weeping forsythiae capsule, fineleaf schizonepeta herb, burdock, lophatherum gracile, fermented soybean, platycodon grandiflorum, liquorice, reed rhizome, peppermint oil, ibuprofen, desloratadine and vitamin C is 170-190: 170-190: 70-75: 100-115: 70-75: 85-95: 100-115: 85-95: 100-115: 1.0 to 1.1: 100-110: 0.5 to 0.7: 48-52;
The auxiliary materials of the compound preparation are cyclodextrin materials, adhesives, diluents, disintegrants, sweeteners, lubricants, coating agents, plasticizers and essence; the weight ratio of the cyclodextrin material to the binder to the diluent to the disintegrating agent to the sweetener to the lubricant to the coating agent to the plasticizer to the essence is 7.2-36: 10 to 52:39 to 198: 6-33: 1 to 5:1 to 6:20 to 105: 5-25: 0.3 to 1.5; the cyclodextrin material is dimethyl-beta-cyclodextrin, and the adhesive comprises the following components in percentage by mass: 0.5-2.5 of low-substituted hydroxypropyl cellulose L11 and povidone K30, wherein the diluent comprises the following components in percentage by mass: 13 to 66: 13-66, mannitol and sorbitol, wherein the disintegrating agent is carboxymethyl starch sodium, the sweetener is sucralose, the lubricant is magnesium stearate, the coating agent is Uttky E12.5, and the plasticizer is diethyl phthalate;
the preparation method of the compound preparation comprises the following steps:
mixing the honeysuckle, the weeping forsythia and the schizonepeta, and extracting by water vapor under the condition that the vacuum degree is-0.04 MPa to-0.09 MPa to obtain volatile oil and dregs;
Mixing the residues with the lophatherum gracile, the fermented soybean, the platycodon grandiflorum, the liquorice and the reed rhizome, and extracting under reduced pressure with water under the conditions of vacuum degree of-0.04 MPa to-0.09 MPa and temperature of 70-80 ℃ to obtain a first filtrate; extracting the burdock with ethanol under reduced pressure at a vacuum degree of-0.04 MPa to-0.09 MPa and a temperature of 60-70 ℃ to obtain a second filtrate; mixing the first filtrate and the second filtrate, concentrating and drying to obtain dry paste powder;
mixing the volatile oil with the peppermint oil and the cyclodextrin material to obtain a volatile oil-peppermint oil cyclodextrin inclusion compound;
mixing, granulating and coating the plasticizer, the coating agent, the dry paste powder, the povidone K30 in the binder and 1/3 of the low-substituted hydroxypropyl cellulose L11 to obtain coated particles of the honeysuckle flower and the forsythia; the mixing, granulating and coating steps comprise: dispersing the plasticizer in the coating agent to obtain a particle coating agent, mixing the dry paste powder with part of the binder, granulating to obtain Yinqiao particles, and coating the Yinqiao particles with the particle coating agent;
mixing 2/3 of the low-substituted hydroxypropyl cellulose L11, the volatile oil-peppermint oil cyclodextrin inclusion compound and the Yinqiao coated particles, which are remained in the ibuprofen, the desloratadine, the vitamin C, the diluent, the disintegrating agent, the sweetener, the lubricant, the essence and the adhesive, and directly tabletting to obtain the compound preparation.
2. The compound preparation of claim 1, wherein the weight ratio of honeysuckle, fructus forsythiae, herba schizonepetae, fructus arctii, lophatherum gracile, fermented soybean, platycodon grandiflorum, liquorice, reed rhizome, peppermint oil, ibuprofen, desloratadine and vitamin C is 180:180:72:108:72:90:108:90:108:1.08:105:0.6:49.5.
3. the preparation method of the compound preparation is characterized by comprising the following steps:
providing the functional ingredient raw materials and auxiliary materials of the compound preparation according to any one of claims 1-2;
mixing the honeysuckle, the weeping forsythia and the schizonepeta, and extracting by water vapor under the condition that the vacuum degree is-0.04 MPa to-0.09 MPa to obtain volatile oil and dregs;
mixing the residues with the lophatherum gracile, the fermented soybean, the platycodon grandiflorum, the liquorice and the reed rhizome, and extracting under reduced pressure with water under the conditions of vacuum degree of-0.04 MPa to-0.09 MPa and temperature of 70-80 ℃ to obtain a first filtrate; extracting the burdock with ethanol under reduced pressure at a vacuum degree of-0.04 MPa to-0.09 MPa and a temperature of 60-70 ℃ to obtain a second filtrate; mixing the first filtrate and the second filtrate, concentrating and drying to obtain dry paste powder;
Mixing the volatile oil with the peppermint oil and the cyclodextrin material to obtain a volatile oil-peppermint oil cyclodextrin inclusion compound;
mixing, granulating and coating the plasticizer, the coating agent, the dry paste powder, the povidone K30 in the binder and 1/3 of the low-substituted hydroxypropyl cellulose L11 to obtain coated particles of the honeysuckle flower and the forsythia;
mixing 2/3 of the low-substituted hydroxypropyl cellulose L11, the volatile oil-peppermint oil cyclodextrin inclusion compound and the Yinqiao coated particles, which are remained in the ibuprofen, the desloratadine, the vitamin C, the diluent, the disintegrating agent, the sweetener, the lubricant, the essence and the adhesive, and directly tabletting to obtain the compound preparation.
4. The method of claim 3, wherein the step of mixing the volatile oil with the peppermint oil and the cyclodextrin material to obtain a volatile oil-peppermint oil cyclodextrin inclusion comprises:
grinding the cyclodextrin in ethanol solution to obtain cyclodextrin ethanol solution; mixing and grinding the cyclodextrin ethanol solution, the volatile oil and the peppermint oil, refrigerating at the temperature of 2-6 ℃ until crystallization is separated out, filtering, washing with 60% ethanol, and drying to obtain the volatile oil-peppermint oil cyclodextrin inclusion compound.
5. The preparation method according to claim 3, wherein the steps of mixing, granulating and coating the plasticizer, the coating agent, the dry paste powder and the povidone K30 and 1/3 of the low-substituted hydroxypropylcellulose L11 in the binder to obtain the coated particles of honeysuckle flower and forsythia comprise;
dispersing the plasticizer in the coating agent to obtain a granule coating agent; mixing the dry paste powder with the povidone K30 and 1/3 of the low-substituted hydroxypropyl cellulose L11 to prepare soft materials, sieving with a 20-mesh sieve to prepare wet particles, drying at 65-75 ℃ until the water content is 3.2-3.6%, and sieving with a 14-mesh sieve to obtain the Yinqiao particles; placing the Yinqiao granules in a coating machine, adjusting the air inlet temperature to 80-90 ℃, the rotating speed of the coating machine to 2-4 rpm/min, preheating to the air outlet temperature to 45-50 ℃, spraying the granule coating agent, gradually increasing the rotating speed to 6-9 rpm/min, increasing the air inlet quantity and the spraying flow of the granule coating agent, and drying the granule surface to obtain the coating agent until all the granule coating agent is used up to obtain the Yinqiao coated granules.
6. The preparation method according to claim 3, wherein the ibuprofen, the desloratadine, the vitamin C, the diluent, the disintegrant, the sweetener, the lubricant, the essence and 2/3 of the remaining low-substituted hydroxypropyl cellulose L11 in the binder are mixed with the volatile oil-peppermint oil cyclodextrin inclusion compound and the Yinqiao coated particles, the sweetener and the essence are added to the desloratadine first, the diluent is added in an equal amount by a gradual addition method, and the ibuprofen, the vitamin C, the Yinqiao coated particles, the volatile oil-peppermint oil cyclodextrin inclusion compound, the remaining low-substituted hydroxypropyl cellulose L11 of 2/3, the disintegrant and the lubricant are continuously added and uniformly mixed.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102614400A (en) * 2012-03-28 2012-08-01 江西济民可信药业有限公司 Preparation method of Chinese herba preparation vitamin C yinqiao tablet
CN103169891A (en) * 2013-04-18 2013-06-26 湖北武当金鼎制药有限公司 Novel vitamin C yinqiao tablet
CN104013841A (en) * 2014-05-30 2014-09-03 广西博科药业有限公司 Preparation method of vitamin C fructus forsythiae capsule
CN110841011A (en) * 2019-12-13 2020-02-28 广东恒诚制药股份有限公司 Vitamin C honeysuckle and forsythia tablet for cold and preparation method thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102614400A (en) * 2012-03-28 2012-08-01 江西济民可信药业有限公司 Preparation method of Chinese herba preparation vitamin C yinqiao tablet
CN103169891A (en) * 2013-04-18 2013-06-26 湖北武当金鼎制药有限公司 Novel vitamin C yinqiao tablet
CN104013841A (en) * 2014-05-30 2014-09-03 广西博科药业有限公司 Preparation method of vitamin C fructus forsythiae capsule
CN110841011A (en) * 2019-12-13 2020-02-28 广东恒诚制药股份有限公司 Vitamin C honeysuckle and forsythia tablet for cold and preparation method thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
关注中西药复方制剂维C银翘片的安全性问题;国家食品药品监督管理局;中国社区医师(第38期);9版 *
增效银翘片治疗感冒275例;王志新,金志甲;陕西中医(第11期);第481-482页 *

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