CN1843505A - Compound Doxycycline lysozyme enteral capsule - Google Patents
Compound Doxycycline lysozyme enteral capsule Download PDFInfo
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- CN1843505A CN1843505A CN 200510033921 CN200510033921A CN1843505A CN 1843505 A CN1843505 A CN 1843505A CN 200510033921 CN200510033921 CN 200510033921 CN 200510033921 A CN200510033921 A CN 200510033921A CN 1843505 A CN1843505 A CN 1843505A
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Abstract
The invention provides a compound enteric coated preparation, which comprises Doxycycline and lysozyme, and can be used for treating upper respiratory tract infection, biliary tract infection, urinary tract infection, senility chronic bronchitis, acute and chronic trachitis, pneumonia, bronchitis and phlegmona caused by sensitized bacterium.
Description
● technical field
The present invention relates to a kind of compound Doxycycline lysozyme enteral preparation, said preparation is used for the treatment of upper respiratory tract infection, biliary tract infection, the urinary tract infection due to the sensitive organism, symptoms such as senile chronic bronchitis, acute and chronic tracheitis, pneumonia, bronchitis, cellulitis clinically.
● invention field
Content of the present invention is to propose a kind of new Doxycycline lysozyme enteral preparation, and this enteric coated preparation can be also enteric coated capsulees of enteric coatel tablets, and this medicament enteric-coated formulation contains doxycycline 20～300mg, lysozyme 20～500mg.Said preparation is used for the treatment of upper respiratory tract infection, biliary tract infection, the urinary tract infection due to the sensitive organism, symptoms such as senile chronic bronchitis, acute and chronic tracheitis, pneumonia, bronchitis, cellulitis clinically.
● background technology
Lysozyme (Lysozyme, Muramidase, Mrcopeptide-N-acetylmuramoylhydrolase, Mucopeptide glycohydrolase, EC3.2.1.17) be human body endogenous organized enzyme, it is widely distributed in the multiple organ-tissues such as people body-centered, liver, spleen, lung, kidney, is a kind of important humoral immunization factor in the human body nonspecific immunity.Discover that lysozyme has stronger killing action to gram positive bacteria, it has good antiviral activity in up-to-date discovering.The antibacterial action of lysozyme is by acting on β-1,4 key between N-acetylglucosamine and the-acetylmuramic acid, make the mucopolysaccharide composition hydrolysis in the bacteria cell wall, cause cell wall rupture, and cellular content is overflowed and made bacterolysis.The lysozyme antivirus action is by combining with electronegative virus protein, form double salt with RNA, DNA, apoprotein, making virally inactivated.Because lysozyme is the non-specific resistance factor of endogenous, so have reasonable safety and anti-drug resistance.At present, because the incidence rate of the drug-resistant bacteria that antibiotic abuse causes improves constantly, make that at present the advantage of the therapeutic effect of lysozyme is more outstanding clinically clinically.But, because lysozyme is protein medicaments, be subjected to the most of inactivation of gastric acid degraded meeting at stomach, simultaneously the stomach absorbtivity again seldom, simple oral formulations is difficult to reach the effect of administration and treatment.Because the oral enteric preparation way has not only solved the difficult problem of oral absorption but also have oral taking convenience, the lysozyme enteric coated preparation is successful clinically at present.
Doxycycline (Doxycycline, claim doxycycline again, doxycycline, DOXICILIN HCL, 6-methyl-4-(dimethylamino)-3,5,10,12,12a,-penta hydroxy group-1,11-dioxo-1,4,4a, 5,5a, 6,11,12a-octahydro-2-aphthacene carboxamide hydrochloride half ethanol semihydrate), being a kind of semi-synthetic Tetracyclines derivant, is that the artificial deoxidation of hydroxyl on 6 of the oxytetracyclines forms this structural variation, on pharmacological properties, show some advantages, antibacterial activity height not only is as Streptococcus hemolyticus, streptococcus pneumoniae, the part gram negative bacteria, the antibacterial activity of vibrio cholera etc. is strong than tetracycline and oxytetracycline, Resistant strain few (still effective to tetracycline resistant bacterial strain such as staphylococcus aureus), there is not obvious cross resistance with natural Tetracyclines, the doxycycline has a broad antifungal spectrum removes common gram-positive cocci, negative bacillus has outside certain antibacterial action, goes back chlamydia, rickettsia, protozoon such as mycoplasma and spirillum has inhibitory action, is commonly used to treat the upper respiratory tract infection due to the sensitive organism clinically, biliary tract infection, urinary tract infection, senile chronic bronchitis, acute and chronic tracheitis, pneumonia, bronchitis, symptoms such as cellulitis.Recent research finds that also except good bacteriostasis, doxycycline also has the anti-reverse transcription effect, and can suppress metalloproteases, decomposes and cancer cell metastasis thereby reduce the cancerous cell gelatin.
After various approach absorbed, its half-life reached 15-22 hour to doxycycline in vivo.It extensively distributes in vivo, liver, kidney, concentration is the highest in bone and the tooth, the metabolism in vivo of doxycycline more than 40%, metabolite does not have microbial activity, and major part is got rid of from feces through bile and intestinal secretion, therefore there is not obvious accumulation phenomena in vivo after the renal insufficiency patient uses this product, so this product is particularly suitable to renal function injury patient's anti-infective therapy.
Because its GI irritation, can cause gastrointestinal reaction and local ulcer, anorexia after the doxycycline ordinary preparation is oral, feel sick, gastrointestinal reactions such as vomiting, stomachache, diarrhoea, for addressing this problem, existing market has also been developed oral doxycycline vibramycin enteric soluble preparation and ejection preparation.
Spain Robert company has developed the compound oral administration preparation (trade name: PULMOTROPIC), be used for the treatment of respiratory tract infection, obtained good effect clinically of lysozyme doxycycline the earliest.We find in the investigation to this kind: doxycycline and lysozyme all are extensive pedigree antibiotics, and both share the antibacterial effect enhancing, except that gram positive bacteria and negative bacterium are had the effect, also can suppress infection such as rickettsia, mycoplasma, virus.Simultaneously, doxycycline has certain antitussive, eliminates the phlegm and antiasthmatic effect, and the upper respiratory tract due to the sensitive organism, senile chronic bronchitis etc. are had curative effect preferably, and is better in treatment chronic bronchitis curative effect.This compound preparation was sold on market nearly more than 20 years, had better curative effect, had obtained to use widely.But because employing is the conventional capsule preparation way, clinical observation is gastrointestinal reaction such as nausea,vomiting,diarrhea to major side effects.
Discover that by clinical pharmacy such side effect mainly is because the doxycycline gastrointestinal reaction in the compound recipe composition causes.Discover that further adopt the conventional capsule preparation way side effect of doxycycline not only can occur, the degraded of gastric acid has simultaneously also reduced the absorption of lysozyme, also find simultaneously, lysozyme in this compound recipe is because be oral difficult absorption of protein event, and onset is slow, and bioavailability is lower.The length and the doxycycline effect is held time, oral post-absorption is very fast, just can bring into play ceiling effect after 3 hours, and effective blood drug concentration is long, is grown up once oral 200 milligrams, discharges in 24 hours to discharge 41% in 32%, 48 hour, is mainly slowly drained by kidney.Therefore what the form of conventional capsule preparation had determined that this oral formulations mode will inevitably cause two kinds of compound recipe compositions can not consistent the acting on of fine performance, that is: lysozyme absorption difference, onset are slow, and doxycycline absorbs fast, the length of holding time, both differences in absorption and metabolism.Simultaneously, also can produce doxycycline gastrointestinal side effect and gastric acid the degraded of lysozyme is made the albumen inactivation.
Find in our research: the compound Doxycycline lysozyme enteral preparation not only can be avoided the generation of doxycycline gastrointestinal side effect, also reduced the absorption that the loss of lysozyme in gastric acid relatively improved lysozyme, also coordinate simultaneously both differences in absorption and metabolism, strengthened the curative effect of this compound recipe greatly.
Enteric coated preparation described in the invention comprises enteric coatel tablets and enteric coated capsule, and said preparation can have the feature of dispersible preparation, can be in intestinal disintegrate fast; Wherein enteric coated capsule can be common enteric coated capsule, also can be the colon enteric coated capsule.
Use conventional method, with the main active of this medicine is that doxycycline and lysozyme mix with pharmaceutic adjuvant, comprising doxycycline hydrochloride 10～1000mg, lysozyme 10～1000mg, filler 0～200mg, disintegrating agent 0～1000mg, wetting agent and lubricant 0～200mg, fluidizer 0～200mg, enteric solubility carrier material 0～500mg, other adjuvants 0～100mg, preparation enteric coated tablet or enteric coated capsule.
Wherein adopting doxycycline and lysozyme in this compound recipe can be the form of the salt that any one can be medicinal, comprises hydrochlorate, acetate, nitrate, nitrite, dithionate, phosphate, benzoate, citrate, fumarate, embonate, tomatotone salt, oxyacetate, mesylate, maleate, to chlorobenzene aminoisobutyric hydrochlorate, formates, lactate, succinate, sulfate, tartrate, cyclohexane-carboxylic acid salt, caproate, caprylate, palmate, the octadecane hydrochlorate, benzene sulfonate, trimethoxybenzoic acid salt, tosilate, the guaiaci lignum hydrochlorate, guaiaci lignum sulfonate, adamantanecarboxylic acid salt, pyrrolidone carboxylic acid salt, naphthalene sulfonate, glucose phosphate salt, glyoxylate, and aspartate, various amino acid salts such as glutamate, Glu.Preferred hydrochlorate, guaiaci lignum hydrochlorate, sulfate, the acetate etc. of adopting.
The lysozyme that is adopted, it can be the lysozyme that variety of way is produced, comprise and from natural plant, animal tissue, extracting, as the lysozyme that extracts from Ovum Gallus domesticus album, or adopt biological engineering method to prepare, as by what from mammal galactophores such as sheep cattle, obtain, also can be that the lysozyme in above-mentioned source passes through chemical modification again in the artificial recombination lysozyme of recombinant expressed productions such as escherichia coli, yeast, Chinese hamster ovary celI or transgenic technology; Can be single aggressiveness, also can be dimer or polymer; Or the form of the various salt of the lysozyme in above-mentioned source, as other forms of slaines such as sodium salt, potassium salt, barium salt, calcium salts, and these salt various hydrates or the crystallization that can form.
Wherein contain the various active component for the treatment of effective dose in the preparation, the weight ratio scope of doxycycline and lysozyme or its officinal salt is 20: 1-1: 20, preferred 5: 1-1: 5.When doxycycline and lysozyme officinal salt were blended in the same unit formulation, active component content preferably adopted the lysozyme of 20～500mg and the doxycycline of 20～300mg in the unit formulation.
Filler can adopt a kind of in starch, pregelatinized Starch, dextrin, Icing Sugar, lactose, mannitol, microcrystalline Cellulose, the calcium sulfate or their mixture.
Disintegrating agent can adopt cellulose derivative (to comprise hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, low replacement-hyprolose, cross-linking sodium carboxymethyl cellulose, carboxy-propyl cellulose, carboxymethylcellulose calcium), polyvinylpolypyrrolidone, starch and derivant thereof, low-substituted hydroxypropyl cellulose, hydroxypropyl starch, modified starch, starch, carboxymethyl starch sodium, microcrystalline Cellulose, crospolyvinylpyrrolidone, tween 80, sodium lauryl sulphate, guar gum, Herba Xanthii glue, a kind of in the xanthan gum or their mixture.
Binding agent can adopt a kind of of starch slurry, hydroxypropyl starch, modified starch, pregelatinized Starch, dextrin, Icing Sugar, syrup, microcrystalline Cellulose, cellulose derivative (comprising hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, ethyl cellulose), polyvinylpyrrolidone rubber cement, gelatine size or their mixture.
Wetting agent, lubricant and fluidizer can adopt a kind of in a kind of in a kind of in water, ethanol or their mixture, magnesium stearate, Pulvis Talci, the hydrogenated vegetable oil or their mixture, modified starch, microcrystalline Cellulose, aluminium hydroxide, boric acid, hydrogenated vegetable oil, Polyethylene Glycol, magnesium stearate, Pulvis Talci, Stepanol MG, sodium lauryl sulphate or the micropowder silica gel or their mixture, micropowder silica gel, the Pulvis Talci or their mixture.
The enteric solubility carrier material comprises cellulose family, as cellulose acetate phthalate ester, hypromellose phthalate ester and carboxylic first and second celluloses; The polyacrylic resin class is as II number and III polyacrylic resin.
Other adjuvants comprise coloring agent, aromatic and sweeting agent, and aromatic and sweeting agent are selected from a kind of in stevioside, glycyrrhizin or Radix Glycyrrhizae extract, essence or the aspartame or their mixture.
The defined medicaments compound according to the present invention can be that the form of pharmaceutical composition exists, and wherein two kinds of active component are that solvent in the same compositions mixes, as compound preparation; Perhaps refer to contain the medicine box of two independent composition components, contain the pharmaceutically acceptable active component of lysozyme enteric coated preparation (comprising enteric coatel tablets/enteric coated capsule) or its arbitrary form or its officinal salt in first compositions as unique active component, contain the active component of doxycycline vibramycin enteric soluble preparation (comprising enteric coatel tablets/enteric coated capsule) or arbitrary forms such as its precursor or metabolite or its officinal salt or one water or many hydrates in second compositions as unique active component., carry out separately when being the Combined drug box form when medication combined,, carry out simultaneously for therapeutic alliance although constitute the administration of two kinds of compositionss of medicine box.
The purposes advantage that the following embodiment of reference is described the application of pharmaceutical composition of the present invention and asked for protection.
● specific embodiments
The preparation of embodiment 1, compound Doxycycline lysozyme enteral capsule
According to any one prescription and method as described below, the preparation compound Doxycycline lysozyme enteral capsule.
The prescription one, under lower temperature and humidity, take by weighing lysozyme 1000g, doxycycline hydrochloride 500g, microcrystalline Cellulose 250g, lactose 1200g, silicon dioxide 50g, cross 80 mesh sieves respectively, place principal agent and adjuvant mixer to mix altogether then, in No. 1 enteric coated capsule of packing into, promptly get compound Doxycycline lysozyme enteral capsule.Make 10000 capsules altogether, every contains doxycycline 50mg and lysozyme 100mg.
Prescription two, under lower temperature and humidity, control moisture, exsiccant condition, get lysozyme powder 150g, doxycycline 75g, pulverized 80 mesh sieves, starch, micropowder silica gel, carboxymethyl cellulose salt, gelatin etc. were fully mixed 80 mesh sieves, abundant mixing, pack in No. 0 capsule, make 1000 capsules altogether, every contains 75mg doxycycline hydrochloride and 150mg lysozyme.
The prescription three, under lower temperature and humidity, get lysozyme 100g, polyacrylic acid II 50g is prepared into microcapsule; Doxycycline hydrochloride 50g, polyacrylic acid II 25g is prepared into microcapsule; Microcrystalline Cellulose 25g, lactose 120g, silicon dioxide 5g cross 80 mesh sieves respectively, place principal agent and adjuvant mixer to mix altogether then, pack in No. 1 capsule, promptly get 1000 compound Doxycycline lysozyme enteral capsules, every contains doxycycline 50mg and lysozyme 100mg.
The prescription four, under lower temperature and humidity, get lysozyme 100g, doxycycline hydrochloride 50g, polyacrylic acid II 75g is prepared into microcapsule; Microcrystalline Cellulose 25g, lactose 120g, silicon dioxide 5g cross 80 mesh sieves respectively, place principal agent and adjuvant mixer to mix altogether then, pack in No. 1 capsule, promptly get compound Doxycycline lysozyme enteral capsule, every contains doxycycline 50mg and lysozyme 100mg.
The prescription five, under lower temperature and humidity, get lysozyme 100g, doxycycline hydrochloride 50g, microcrystalline Cellulose 25g, lactose 120g, silicon dioxide 5g crosses 80 mesh sieves respectively, polyacrylic acid II 150g is prepared into microcapsule, places principal agent and adjuvant mixer to mix altogether then, in incapsulating, promptly get compound Doxycycline lysozyme enteral capsule.Every contains doxycycline 50mg and lysozyme 100mg.
The prescription six, under lower temperature and humidity, get lysozyme 100g, doxycycline hydrochloride 50g, microcrystalline Cellulose 25g, lactose 120g, silicon dioxide 5g cross 80 mesh sieves respectively, place principal agent and adjuvant mixer to mix altogether then, the parcel enteric material in incapsulating, promptly gets compound Doxycycline lysozyme enteral capsule.Every contains doxycycline 50mg and lysozyme 100mg.
The prescription seven, under lower temperature and humidity, getting lysozyme 100g, doxycycline 50g, carboxymethyl cellulose salt 15g, low-substituted hydroxypropyl cellulose 15g, cross-linked pvp 10g, gelatin 5g etc. fully mixes, be prepared into microcapsule, then microcapsule and microcrystalline Cellulose 5g, starch 25g, Pulvis Talci are fully mixed, the capsule of packing into No. 1, be prepared into 1000 enteric coated capsulees, every contains 100mg lysozyme and 50mg doxycycline.
Prescription eight, under lower temperature and humidity, take by weighing lysozyme 100g, lactose 50g crosses 80 mesh sieves respectively, fully mixes, and adds binding agent then and makes soft material in right amount, granulate, oven dry, granulate, stand-by; Doxycycline hydrochloride 50g, polyvinylpolypyrrolidone 50g, microcrystalline Cellulose 50g, cross 80 mesh sieves respectively, fully mix, add binding agent then and make soft material in right amount, granulate, oven dry, granulate fully mixes the lysozyme granule with the doxycycline granule, in the enteric coated capsule of packing into, make 1000 enteric coated capsulees altogether, every contains 100mg lysozyme and 50mg doxycycline.
The antiacid performance measurement of example 2, compound doxycycline enteric coated capsule
With compound Doxycycline lysozyme enteral capsule (lot number: 041001,041002,041003) be positioned in the 100ml simulated gastric fluid, mixing speed is no more than 200r/min in 37 ± 1 ℃ water bath with thermostatic control, in 2 hours, measure enteric coated capsule content doxycycline burst size, 10 (n=10) of every lot number sample sampling, the doxycycline content that adopts the HPLC method to measure in the solution is also compared with doxycycline total content in the capsule, found that three batch sample doxycycline burst sizes are 5.07 ± 2.6%.
1, the enteric performance of enteric coated capsule
With compound Doxycycline lysozyme enteral capsule (lot number: 041001,041002,041003) be positioned in the 100ml simulated intestinal fluid, mixing speed is no more than 200r/min in 37 ± 1 ℃ water bath with thermostatic control, in 1 hour, measure enteric coated capsule content doxycycline burst size, 10 (n=10) of every lot number sample sampling, the doxycycline content that adopts the HPLC method to measure in the solution is also compared with doxycycline total content in the capsule, found that the average burst size of doxycycline in the enteric coated capsule is 97.3 ± 4.8% in three batch samples.
2, the stability of enteric coated capsule
Put into saturated nacl aqueous solution in the exsiccator bottom, top put 3 batches (lot number: 041001,041002,041003) compound Doxycycline lysozyme enteral capsule sample, seal, exsiccator is put in 40 ± 1 ℃ of constant incubators continuously and placed 90 days, every sampling in 30 days once, measure.
Table one, constant temperature and humidity accelerated test result (40 ± 1 ℃ of temperature, humidity 75%)
| Time (my god) | Outward appearance | In the gastric juice (2h) | Disintegrate in the intestinal juice (T/min) | Labelled amount/% |
| 0 | No change | Not disintegrate | 29.3±0.9 | 103.8±0.9 |
| 30 | No change | Not disintegrate | 29.7±1.8 | 98.2±1.5 |
| 60 | No change | Not disintegrate | 29.4±1.6 | 107.3±4.2 |
| 90 | No change | Not disintegrate | 29.0±1.4 | 103.5±5.4 |
The preparation of example 3, compound Doxycycline lysozyme enteral sheet
According to any one prescription and method as described below, preparation compound Doxycycline lysozyme enteral tablet.
The prescription one, under lower temperature and humidity, take by weighing lysozyme 100g, doxycycline hydrochloride 50g, microcrystalline Cellulose 25g, lactose 120g, silicon dioxide 5g, cross 80 mesh sieves respectively, fully mix, add binding agent then and make soft material in right amount, granulate, oven dry, granulate, add again be pressed into the tablet of 300mg behind 0.1% the magnesium stearate mix homogeneously after, promptly get the compound Doxycycline lysozyme enteral tablet with the enteric material coating, every contains doxycycline 50mg and lysozyme 100mg.
The prescription two, under lower temperature and humidity, take by weighing lysozyme 150g, doxycycline hydrochloride 75g, microcrystalline Cellulose 40g, starch 180g, silicon dioxide 5g, cross 80 mesh sieves respectively, fully mix, add binding agent then and make soft material in right amount, granulate, oven dry, granulate, add again be pressed into the tablet of 450mg behind 0.1% the Pulvis Talci mix homogeneously after, promptly get the compound Doxycycline lysozyme enteral tablet with the enteric material coating, every contains doxycycline 75mg and lysozyme 150mg.
The prescription three, under lower temperature and humidity, get lysozyme 100g, polyacrylic acid II 50g is prepared into microcapsule; Doxycycline hydrochloride 50g, polyacrylic acid II 25g is prepared into microcapsule; Calcium sulfate 30g, dextrin 120g, cross 80 mesh sieves respectively, add binding agent then and make soft material in right amount, granulate, oven dry, granulate, add again be pressed into the tablet of 300mg behind 0.1% the magnesium stearate mix homogeneously after, promptly get the compound Doxycycline lysozyme enteral tablet with the enteric material coating, every contains doxycycline 50mg and lysozyme 100mg.
The prescription four, under lower temperature and humidity, get lysozyme 100g, doxycycline hydrochloride 50g, polyacrylic acid III 75g is prepared into microcapsule; Microcrystalline Cellulose 25g, mannitol 120g, silicon dioxide 5g crosses 80 mesh sieves respectively, add binding agent then and make soft material in right amount, granulate, oven dry, granulate, add again be pressed into the tablet of 300mg behind 0.1% the hydrogenated vegetable oil mix homogeneously after, promptly get the compound Doxycycline lysozyme enteral tablet with the enteric material coating, every contains doxycycline 50mg and lysozyme 100mg.
The prescription five, under lower temperature and humidity, get lysozyme 100g, doxycycline hydrochloride 50g, microcrystalline Cellulose 25g, lactose 120g, silicon dioxide 5g cross 80 mesh sieves respectively, place principal agent and adjuvant mixer to mix altogether then, add again directly be pressed into the tablet of 300mg after 0.1% magnesium stearate is mixed after, promptly get the compound Doxycycline lysozyme enteral tablet with the enteric material coating, every contains doxycycline 50mg and lysozyme 100mg.
The prescription six, under lower temperature and humidity, take by weighing lysozyme 150g, doxycycline hydrochloride 75g, microcrystalline Cellulose 40g, lactose 180g, silicon dioxide 5g, cross 80 mesh sieves respectively, add again be pressed into the tablet of 450mg behind 0.1% the magnesium stearate mix homogeneously after, promptly get the compound Doxycycline lysozyme enteral tablet with the enteric material coating, every contains doxycycline 75mg and lysozyme 150mg.
The prescription seven, under lower temperature and humidity, getting lysozyme 100g, doxycycline 50g, carboxymethyl cellulose salt 15g, low-substituted hydroxypropyl cellulose 15g, cross-linked pvp 10g, gelatin 5g etc. fully mixes, be prepared into microcapsule, then microcapsule and microcrystalline Cellulose 5g, starch 25g, Pulvis Talci are fully mixed, add again directly be pressed into the tablet of 225mg after 0.1% magnesium stearate is mixed after, promptly get the compound Doxycycline lysozyme enteral tablet with the enteric material coating, every contains doxycycline 50mg and lysozyme 100mg.
Prescription eight, under lower temperature and humidity, take by weighing lysozyme 100g, lactose 50g crosses 80 mesh sieves respectively, fully mixes, and adds binding agent then and makes soft material in right amount, granulate, oven dry, granulate, stand-by; Doxycycline hydrochloride 50g, polyvinylpolypyrrolidone 50g, microcrystalline Cellulose 50g crosses 80 mesh sieves respectively, fully mixes, and adds binding agent then and makes soft material in right amount, granulates oven dry, granulate; Lysozyme granule and doxycycline granule are fully mixed, add again directly be pressed into the tablet of 350mg after 0.1% magnesium stearate is mixed after, promptly get the compound Doxycycline lysozyme enteral tablet with the enteric material coating, every contains doxycycline 50mg and lysozyme 100mg.
Claims (7)
1. the enteric coated preparation of a compound doxycycline lysozyme, it is characterized in that containing doxycycline and lysozyme, be used for the treatment of upper respiratory tract infection, biliary tract infection, urinary tract infection due to the sensitive organism clinically, symptoms such as senile chronic bronchitis, acute and chronic tracheitis, pneumonia, bronchitis, cellulitis.
2. enteric coated preparation according to claim 1, it is characterized in that used doxycycline and lysozyme can be the forms of the salt that any one can be medicinal, comprise hydrochlorate, acetate, nitrate, nitrite, dithionate, phosphate, benzoate, citrate, fumarate, embonate, tomatotone salt, oxyacetate, mesylate, maleate, to chlorobenzene aminoisobutyric hydrochlorate, formates, lactate, succinate, sulfate, tartrate, cyclohexane-carboxylic acid salt, caproate, caprylate, palmate, the octadecane hydrochlorate, benzene sulfonate, trimethoxybenzoic acid salt, tosilate, the guaiaci lignum hydrochlorate, guaiaci lignum sulfonate, adamantanecarboxylic acid salt, pyrrolidone carboxylic acid salt, naphthalene sulfonate, glucose phosphate salt, glyoxylate, and aspartate, various amino acid salts such as glutamate, Glu.Preferred hydrochlorate, guaiaci lignum hydrochlorate, sulfate, the acetate etc. of adopting.
3. enteric coated preparation according to claim 1, it is characterized in that the lysozyme that adopted, it can be the lysozyme that variety of way is produced, comprise and from natural plant, animal tissue, extracting, as the lysozyme that extracts from Ovum Gallus domesticus album, or adopt biological engineering method to prepare, as by what from mammal galactophores such as sheep cattle, obtain, also can be that the lysozyme in above-mentioned source passes through chemical modification again in the artificial recombination lysozyme of recombinant expressed productions such as escherichia coli, yeast, Chinese hamster ovary celI or transgenic technology; Can be single aggressiveness, also can be dimer or polymer; Or the form of the various salt of the lysozyme in above-mentioned source, as other forms of slaines such as sodium salt, potassium salt, barium salt, calcium salts, and these salt various hydrates or the crystallization that can form.
4. enteric coated preparation according to claim 1 is characterized in that said preparation can be enteric coatel tablets or enteric coated capsule, and said preparation can have the feature of dispersible preparation, can be in intestinal disintegrate fast; Wherein enteric coated capsule can be common enteric coated capsule, also can be the colon enteric coated capsule.
5. enteric coated preparation according to claim 1, it is characterized in that it to be the enteric coatel tablets that adopt the mode coated outside enteric material preparation of common oral preparation, or the enteric coated capsule of the preparation way preparation of employing fill enteric capsule shell, it also can be the doxycycline that adopts the enteric technology to granulate, the enteric-coated microcapsule of lysozyme or microgranule, or coat enteric coating outward, then microcapsule/microgranule is prepared into enteric coatel tablets or be placed on common or the enteric solubility capsule in, its preparation method also can be, with both doxycycline, lysozyme is made microcapsule or microgranule separately, mixes with adjuvant again; Make microcapsule again after also doxycycline and lysozyme can being mixed earlier or microgranule mixes with adjuvant; Doxycycline, lysozyme, adjuvant three can also be made microcapsule or microgranule after mixing, reinstall in the capsule or and adjuvant mixed pressuring plate.Also can be doxycycline and lysozyme are prepared into respectively little common or/and enteric coated capsule is mounted on a big enteric or/and in the conventional capsule with two little enteric coated capsulees again.
6. enteric coated preparation according to claim 1, it is characterized in that containing in the per unit preparation doxycycline 10～1000mg, lysozyme 10～1000mg and pharmaceutic adjuvant, described pharmaceutic adjuvant comprises filler 0～200mg, disintegrating agent 0～1000mg, wetting agent and lubricant 0～200mg, fluidizer 0～200mg, enteric solubility carrier material 0～500mg, other adjuvants 0～100mg.The preferred employing contained doxycycline 20～300mg, lysozyme 20～500mg.
7. enteric coated preparation according to claim 6, wherein said filler are selected from a kind of in starch, pregelatinized Starch, dextrin, Icing Sugar, lactose, mannitol, microcrystalline Cellulose, the calcium sulfate or their mixture.Disintegrating agent is selected from cellulose derivative and (comprises hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, low replacement-hyprolose, cross-linking sodium carboxymethyl cellulose, carboxy-propyl cellulose, carboxymethylcellulose calcium), polyvinylpolypyrrolidone, starch and derivant thereof, low-substituted hydroxypropyl cellulose, hydroxypropyl starch, modified starch, starch, carboxymethyl starch sodium, microcrystalline Cellulose, crospolyvinylpyrrolidone, tween 80, sodium lauryl sulphate, guar gum, Herba Xanthii glue, a kind of in the xanthan gum or their mixture.Binding agent is selected from a kind of of starch slurry, hydroxypropyl starch, modified starch, pregelatinized Starch, dextrin, Icing Sugar, syrup, microcrystalline Cellulose, cellulose derivative (comprising hydroxypropyl emthylcellulose, methylcellulose, sodium carboxymethyl cellulose, ethyl cellulose), polyvinylpyrrolidone rubber cement, gelatine size or their mixture.Wetting agent, lubricant and fluidizer are selected from a kind of in water, ethanol or their mixture, magnesium stearate, Pulvis Talci, the hydrogenated vegetable oil or their mixture, and a kind of in modified starch, microcrystalline Cellulose, aluminium hydroxide, boric acid, hydrogenated vegetable oil, Polyethylene Glycol, magnesium stearate, Pulvis Talci, Stepanol MG, sodium lauryl sulphate or the micropowder silica gel or their mixture, also have a kind of in micropowder silica gel, the Pulvis Talci or their mixture.The enteric solubility carrier material comprises cellulose family, as cellulose acetate phthalate ester, hypromellose phthalate ester and carboxylic first and second celluloses; The polyacrylic resin class is as II number and III polyacrylic resin.Other adjuvants comprise coloring agent, aromatic and sweeting agent, and aromatic and sweeting agent are selected from a kind of in stevioside, glycyrrhizin or Radix Glycyrrhizae extract, essence or the aspartame or their mixture.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101905025A (en) * | 2010-07-20 | 2010-12-08 | 浙江大学 | Preparation method for protective agent of intestinal mucosal barrier |
| CN102675145A (en) * | 2012-04-27 | 2012-09-19 | 山东恩康药业有限公司 | Preparation method of guaiacol sulfonate doxycycline |
| CN105854748A (en) * | 2016-06-02 | 2016-08-17 | 天津工业大学 | Method for preparing cellulose acetate capsule with concave surface structure |
| CN106580890A (en) * | 2017-01-02 | 2017-04-26 | 武汉新联大生物有限公司 | Doxycycline hydrochloride solid dispersant for animals, and preparation method thereof |
| CN108272813A (en) * | 2018-03-30 | 2018-07-13 | 浙江惠松制药有限公司 | It is a kind of to be used to mitigate pharmaceutical composition and its granule preparation method, the detection method and application that terramycin induced Vomiting reacts |
| CN108602761A (en) * | 2015-11-24 | 2018-09-28 | 好利安科技有限公司 | The salt of Tetracyclines |
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2005
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101905025A (en) * | 2010-07-20 | 2010-12-08 | 浙江大学 | Preparation method for protective agent of intestinal mucosal barrier |
| CN102675145A (en) * | 2012-04-27 | 2012-09-19 | 山东恩康药业有限公司 | Preparation method of guaiacol sulfonate doxycycline |
| CN108602761A (en) * | 2015-11-24 | 2018-09-28 | 好利安科技有限公司 | The salt of Tetracyclines |
| JP2019503993A (en) * | 2015-11-24 | 2019-02-14 | ホビオネ サイエンティア リミテッド | Tetracycline salt |
| CN105854748A (en) * | 2016-06-02 | 2016-08-17 | 天津工业大学 | Method for preparing cellulose acetate capsule with concave surface structure |
| CN105854748B (en) * | 2016-06-02 | 2018-07-31 | 天津工业大学 | A kind of preparation method of surface concave structure acetate fiber cellulose capsule |
| CN106580890A (en) * | 2017-01-02 | 2017-04-26 | 武汉新联大生物有限公司 | Doxycycline hydrochloride solid dispersant for animals, and preparation method thereof |
| CN108272813A (en) * | 2018-03-30 | 2018-07-13 | 浙江惠松制药有限公司 | It is a kind of to be used to mitigate pharmaceutical composition and its granule preparation method, the detection method and application that terramycin induced Vomiting reacts |
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