CN1569224A - Interferon effervescence capsule for vagina used and its preparation method - Google Patents
Interferon effervescence capsule for vagina used and its preparation method Download PDFInfo
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Abstract
The invention relates to an interferon vaginal effervescence capsule and its preparation process. It is composed of interferon, adjuvant with water solubility, effervescence disintegrating agent, auxiliary disintegrating agent and adhesive. The capsule formulation has advantages of simple preparation, convenient medicine taking, rapid disintegrating, effervescing rapidly to cover the injury surface and release medicine, having no pollution to clothes, favorable uniformity and stability. It has favorable therapeutic functions for cervicitis and cervical erosion.
Description
Technical field
The present invention relates to drug world.Be specifically related to a kind of interferon vagina effervescent capsule and preparation method.
Background technology
Interferon has disease-resistant element, anti-cell hypertrophy and immunoregulatory effect, so after it is found, become the active drug that can be widely used in treating viral disease and some tumor so far, for example treat viral hepatitis, herpes zoster, poliomyelitis virus, Coxsackie virus, influenza virus ... or the like.
Chronic cervicitis, cervical erosion are common gynecological disease, frequently-occurring disease, and the married woman has the puzzlements that are subjected to this disease more than half approximately.Study carefully its pathogenic factor, mostly be due to HPV-16, the HPV-18 infection, and for bringing out the high risk factor of cervical cancer.Because interferon is a kind of bioactive substance, have to light, thermo-responsive and under liquid condition unsettled characteristic, the vagina medicinal thing of how it is prepared into stable, homogeneous, treating the gynaecopathia toxinfection efficiently, easily promptly becomes the target of development.The dosage form of present domestic most interferon is dosage forms such as injection, suppository, eye drop, tablet, gel, spray, but up to the present, do not find a kind of interferon effervescent capsule preparations that aims at treatment female chronic cervicitis, cervical erosion as yet for vagina administration.
What describe among the Chinese patent application CN1284381 disclosed " recombined human interferon alpha gel preparation and production method " is to be prepared into semisolid gel-type preparation, wherein contain a large amount of moisture, cause the hydrolytic degradation effect of interferon protein active component easily, also have to add the chemical substance that interferon is had infringement such as the antiseptic of sodium benzoate etc. in addition.Chinese patent application CN1324659 provides " a kind of vagina spray that contains bioactie agent " for this reason, this invention for avoid interference plain in solution contingent unstable factor, proposed to join in another part Chinese medicine extraction solution and go facing dried ingredients that the time spent just will contain the interferon raw material.Therefore from improving the dosage form of interferon formulation stability, it is more favourable adopting injectable powder usually.But injectable powder is to need the drug administration by injection mode, has some inconvenient defectives.
Adopt suppository formulation, reduce the adverse effect of moisture content, help vagina administration approach and local therapeutic effect, as Chinese patent application CN1315206 " interferon suppository and production method thereof ", CN1105849 " hard porous foam embolus and manufacturing process thereof " description is a kind of process for preparing interferon suppository.But the process that interferon will be put into fused suppository base mix homogeneously is all arranged in its technology, and the melt temperature of this moment may cause that the heat inactivation that is subjected to of interferon protein active component influences.
CN1140088A " LeIF buccal tablet and method for making thereof ", CN1227124A " beta interferon lozenge and preparation method thereof " are disclosed to be the Peroral solid dosage form tablet, CN1381273 " vaginal-applied interferon table and preparation technology " is disclosed to be the solid tablet of vagina administration, when these all help avoiding moisture content to store to the influence of interferon.But in preparation process, all must stand quite big pressure to containing the intensive pressurized effect of interferon raw material part, may cause the adverse effect of interferon activity component portion inactivation.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of effervescent capsule of vaginal-applied interferon, it is simple that this capsule has technology, and medication is convenient, disintegrate and effervescent wound coverage face release medicine fast rapidly, pollution clothes not, the characteristics of uniformity and good stability.
Interferon vagina effervescent capsule prescription percentage by weight prescription disclosed by the invention consists of:
The amounts of components scope
Interferon 4 * 10
9IU～11 * 10
9IU
Water soluble adjuvant 16%～84%
Gas-producing disintegrant 2%～67%
Complementary disintegrating agent 0～20%
Binding agent is an amount of
Make 10000 capsules
Interferon of the present invention is natural or Interferon Alfa-2b, and analog.
Water soluble adjuvant of the present invention can be selected from one or more mixture of lactose, mannitol, glucose, sorbitol etc.
Gas-producing disintegrant of the present invention can be selected from carbonate and acid, and wherein carbonate comprises sodium carbonate, sodium bicarbonate, calcium carbonate, potassium carbonate or potassium bicarbonate etc.; Acid comprises malic acid, citric acid, tartaric acid, alginic acid or boric acid etc.
Binding agent of the present invention is optional from polyethylene pyrrolidone, hydroxypropyl emthylcellulose or ethanol etc.
Complementary disintegrating agent of the present invention for commonly used pharmaceutic adjuvant as starch, pregelatinized Starch, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crosslinked polyethylene pyrrolidone or cross-linking sodium carboxymethyl cellulose etc.
Another technical problem to be solved by this invention is to disclose the capsular preparation method of above-mentioned interferon vagina effervescent.
The capsular preparation of interferon vagina effervescent disclosed by the invention comprises the following steps:
(1) preparation interferon particles
The dissolved dilution in solvent medium with interferon or its analog, add the part water soluble adjuvant, behind the mix homogeneously, vacuum drying, baking temperature be controlled at subzero 30 ℃ to 25 ℃ of scopes of room temperature, make the solids that contains principal agent, and then with the principle of equivalent incremental method, append the part water soluble adjuvant, after amplifying dilution the interferon powder particle, detect the granule water content and the uniformity and answer requirement up to specification, and measure interferon content;
(2) preparation effervescent particulate
With the gas-producing disintegrant mix homogeneously of carbonate and acid, add an amount of binding agent and carry out mixing granulation, make the granules of accessories particle size range of effervescent disintegrate account for 1%-30% less than 75 μ m, account for 5%-50% greater than 300 μ m;
(3) granule that step (1) and (2) are made adds complementary disintegrating agent, and mix homogeneously, the moisture content of total mixture are controlled in 0.2～5.0% scope, and filled capsules promptly.
Solvent for use comprises purified water, buffer solution etc. in the inventive method, and wherein buffer solution can be selected from borate buffer solution, phosphate buffer solution, and citric acid solution or acetic acid buffer solution etc., its pH value is between 3.0-8.0.
The present invention with this proteinoid of Interferon Alpha-2b (polypeptide) material after above-mentioned PROCESS FOR TREATMENT; make the raw material medicated powder of larger volume; with other pharmaceutic adjuvant mix homogeneously; incapsulate; reached the purpose that makes the basic non-inactivation of Interferon Alpha-2b, good uniformity, and the protection medicine is not subjected to the influence of light, dampness.
Interferon vagina effervescent capsule of the present invention is carried out the test of disintegration and dissolution, and the result shows that effervescent capsule of the present invention disintegrate is rapid, and stripping is complete, sees Table 1, table 2.
Table 1 Interferon Alpha-2b vagina effervescent capsule summary sheet disintegration
| Lot number | Specification | Disintegration (branch) | |||||
| ????1 | ??2 | ??3 | ??4 | ??5 | ??6 | ||
| 990301 | 800,000 IU/ grains | ?5’05” | 5’10” | 4’50” | 5’08” | 5’11” | 5’09” |
| 990302 | 800,000 IU/ grains | ?5’07” | 5’20” | 5’19” | 5’13” | 5’15” | 5’22” |
| 990303 | 800,000 IU/ grains | ?5’12” | 5’30” | 5’22” | 5’18” | 5’12” | 5’17” |
| 010601 | 800,000 IU/ grains | ?6’07” | 6’10” | 6’12” | 6’18” | 6’20” | 6’12” |
The off-bottom of 15 minutes glue shells
Table 2 Interferon Alpha-2b vagina effervescent capsule stripping situation summary sheet
Illustrate: (1) sample stripping situation is with the biological activity determination data representation
(2) sample sampling in 10 minutes after the disintegrate in 37 ± 1 ℃ of lysates, respectively
Measure tiring of every increment basis
| Lot number | Specification | Biological activity (* 10 5The IU/ grain) | |||||||
| ??1 | ???2 | ???3 | ???4 | ???5 | ???6 | ???7 | ?????8 | ||
| ?990311 | 400,000 IU/ grains | ?6.63 | ??4.62 | ??6.10 | ??4.14 | ??6.53 | ??3.18 | ??3.93 | ?????- |
| ?990322 | 400,000 IU/ grains | ?5.32 | ??5.32 | ??4.77 | ??5.05 | ??6.94 | ???- | ???- | ?????- |
| ?990301 | 800,000 IU/ grains | ?9.02 | ??8.66 | ??9.16 | ??9.67 | ??8.19 | ??8.67 | ??8.20 | ????10.1 |
| ?990302 | 800,000 IU/ grains | ?8.67 | ??7.24 | ??8.08 | ??8.33 | ??9.67 | ??8.15 | ??7.76 | ????9.29 |
| ?990303 | 800,000 IU/ grains | ?9.68 | ??8.19 | ??7.33 | ??8.54 | ??9.16 | ??8.42 | ??9.94 | ????8.67 |
| ?010601 | 800,000 IU/ grains | ?8.79 | ??8.32 | ??8.20 | ??8.55 | ??9.29 | ??8.00 | ??8.67 | ????8.43 |
| ?96011 | 400,000 IU/ grains | ?4.12 | ??4.15 | ??4.47 | ??4.62 | ??4.34 | ??4.18 | ??3.62 | ????4.01 |
| ?96012 | 400,000 IU/ grains | ?4.05 | ??4.12 | ??4.54 | ??4.28 | ??4.21 | ??4.49 | ??3.88 | ????4.03 |
| ?96013 | 400,000 IU/ grains | ?4.12 | ??4.01 | ??4.35 | ??4.41 | ??4.19 | ??4.25 | ??3.98 | ????4.07 |
Interferon vagina effervescent capsule of the present invention is carried out the study on the stability test, the result shows that effervescent capsule of the present invention is long-term tests in 2 years of 25 ℃, 37 ℃ continuous 6 months accelerated tests and 2-8 ℃ through temperature, it is tired (biological activity) and outward appearance there is no significant change, see Table 3-1,3-2,3-3, embodied good stable.
Table 3-1 Interferon Alpha-2b vagina effervescent capsule stability is investigated summary sheet as a result
Accelerated test: 25 ℃ of temperature
| Lot number | Observation item | Observed result (ten thousand IU/ grains) | ||||
| 0 month | January | February | March | June | ||
| 990,301 80 ten thousand IU/ grains | Outward appearance | Hard capsule, white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire | ??90.2 | ???87.7 | ???87.7 | ???104.0 | ???99.3 | |
| 990,302 80 ten thousand IU/ grains | Outward appearance | Hard capsule, white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire | ??94.0 | ???94.0 | ???87.7 | ???116.0 | ???91.4 | |
| 990,303 80 ten thousand IU/ grains | Outward appearance | Hard capsule, white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire | ??104.0 | ???91.4 | ???106.0 | ???88.8 | ???93.9 | |
Table 3-2 accelerated test: 37 ℃ of temperature
| Lot number | Observation item | Observed result (ten thousand IU/ grains) | ||||
| 0 month | January | February | March | June | ||
| 990,301 80 ten thousand IU/ grains | Outward appearance | Hard capsule, white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire | ??90.2 | ??87.7 | ??86.5 | ??111.0 | ??96.7 | |
| 990,302 80 ten thousand IU/ grains | Outward appearance | Hard capsule, white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire | ??94.0 | ??96.6 | ??84.1 | ??97.8 | ??89.0 | |
| 990,303 80 ten thousand IU/ grains | Outward appearance | Hard capsule, white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire | ??104.0 | ??92.7 | ??88.9 | ??103.0 | ??92.8 | |
Table 3-3 Interferon Alpha-2b vagina effervescent capsule stability is investigated summary sheet as a result
Long term test: 4 ℃ of temperature
| Lot number | Specification (ten thousand IU/ grains) | The investigation project | Observed result |
| 0 month | March | June | JIUYUE | December | 15 months | 18 months | 24 months | |||
| 1 | ?40 | Outward appearance | The content of hard capsule is white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire (ten thousand IU/ grains) | ????41.2 | ??41.5 | ??44.7 | ??46.2 | ??43.4 | ??41.8 | ??36.2 | ??40.1 | ||
| Dissolution | ?????- | ???- | ???- | ???- | ???- | Qualified | Qualified | Qualified | ||
| 2 | ?40 | Outward appearance | The content of hard capsule is white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire (ten thousand IU/ grains) | ????40.5 | ??41.2 | ??45.4 | ??42.8 | ??42.1 | ??44.9 | ??38.8 | ??40.3 | ||
| Dissolution | ?????- | ???- | ???- | ???- | ???- | Qualified | Qualified | Qualified | ||
| 3 | ?40 | Outward appearance | The content of hard capsule is white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire (ten thousand IU/ grains) | ????41.2 | ??40.1 | ??43.5 | ??44.1 | ??41.9 | ??42.5 | ??39.8 | ??40.7 | ||
| Dissolution | ?????- | ???- | ???- | ???- | ???- | Qualified | Qualified | Qualified | ||
| 4 | ?80 | Outward appearance | The white corase meal of hard capsule | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire (ten thousand IU/ grains) | ????90.2 | ?104.0 | ??98.1 | ??96.7 | ??92.7 | ??91.2 | ??89.9 | ??90.1 | ||
| 5 | ?80 | Outward appearance | The white corase meal of hard capsule | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire (ten thousand IU/ grains) | ????94.0 | ?100.0 | ??95.4 | ??102.0 | ??92.7 | ??88.7 | ??86.2 | ??96.6 | ||
| 6 | ?80 | Outward appearance | The content of hard capsule is white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire (ten thousand IU/ grains) | ???104.0 | ??98.0 | ??92.8 | ??105.0 | ??98.0 | ??86.3 | ??92.4 | ??100.0 |
| ??7 | ??80 | Outward appearance | The content of hard capsule is white corase meal | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation | Do not see variation |
| Tire (ten thousand IU/ grains) | ????94.0 | ??91.5 | ???89.0 | ??91.4 | ??80.7 | ??- | ??88.0 | ??70.3 |
A technical problem more to be solved by this invention is to disclose the application of above-mentioned interferon vagina effervescent capsule in preparation treatment cervicitis, cervical erosion medicine.
Interferon vagina effervescent capsule transvaginal of the present invention administration, absorb by the vaginal mucosa epithelium, directly at part performance antivirus action, enter an intravital interferon part through protease hydrolysis, another part excretes through the urine prototype, and cervicitis, cervical erosion are had good therapeutic effect.
Effervescent capsule of the present invention is carried out general pharmacology learns test, acute toxicity test, long term toxicity test and vagina local excitation test:
1. general pharmacology is learned test
Intravaginal administration is under the condition of 5 times (33500IU/kg is called for short low dosage) and 50 times (335000IU/kg is called for short high dose) of clinical dosage (6700IU/kg), (same dosage is all used in following test).Material: animal ICR mice, body weight 19-21 gram, male and female half and half, SD rat body weight 160-175 restrains male and female half and half; Cat 2.9 ± 0.9kg.
(1) to the influence of spontaneous activity in mice
Behind the vagina administration 60 minutes, observe spontaneous activity in mice number of times in 10 minutes.
Result: 394 ± 95 times/10min of matched group; 406 ± 101 times/10min of high dose group; 388 ± 115 times/10min of low dose group, no matter the administration group is that high dose, low dosage and matched group compare, its spontaneous activity number of times does not have the statistics difference, P＞0.05.
(2) to the influence of amfetamine central excitation effect
Vagina administration 60 minutes, 8 milligrams/kg of subcutaneous injection amfetamine, record spontaneous activity in mice number of times after 15 minutes.
The result: respectively organizing the spontaneous activity in mice number of times behind the benzene injection propylamine obviously increases, and has compared remarkable biological significance with matched group, P＜0.01, but with amfetamine each the group, its spontaneous activity does not have the statistics difference, P＞0.05.
(3) to the influence of mouse sleep time
Behind the vagina administration 60 minutes, respectively from lumbar injection pentobarbital sodium 50mg/kg, with mice areflexia and the index of recovering as the length of one's sleep.
The result: no matter the mice of vagina administration group and injection pentobarbital sodium is high dose group or low dose group, and mouse sleep time is compared with the pentobarbital sodium value, does not all have the statistics difference, P＞0.05.
(4) to the influence of mice strychnine convulsions effect
Behind the vagina administration 60 minutes, subcutaneous injection strychnine 1mg/kg observes the time that convulsions occurs.
The result: the vagina administration group does not influence the convulsions response time of strychnine, no statistics difference, P＞0.05.
(5) to the influence of rat temperature
Respectively survey one time the anus temperature behind the vagina administration 60 minutes, 120 minutes, 240 minutes the time.
Result: respectively organize rat anus Wen Junwu statistics difference, P＞0.05 before and after the administration.
(6) to the influence of anesthetized cat blood pressure
Observe blood pressure, breathing, heart rate influence in 300 minutes behind the vagina administration.
The result: comparing with matched group does not all have the statistics difference, P＞0.05.
2. rabbit acute toxicity test
The vagina single administration reaches 1000 times of clinical dosage, observes 14 days.
The result: place no abnormality seen reaction behind the vagina, its general activity, appetite, feces are normal, observe and do not see death in 14 days.
3. rat long term toxicity test
Vagina administration is equivalent to 50 times, 25 times and 5 times of clinical dosage, and successive administration 90 days is also observed the general symptom of rat, blood parameters and the pathological examination of 30 days convalescent periods.
(1) general observation of symptoms
Outward appearance body weight, feed consumption are compared no significant difference with matched group, P＞0.05.
(2) mensuration such as peripheral hemogram leukocyte, erythrocyte, platelet, coagulation function show, no matter are during 90 days administration or convalescent 30 days, and each group inspection all in normal range, does not all have the statistics difference, P＞0.05.
(3) blood parameters is measured
Hepatic and renal function, blood fat, white/globulin and electrolytes determined measure to show no matter be during 90 days administration or convalescent 30 days, and each group inspection all in normal range, does not all have the statistics difference, P＞0.05.
(4) pathological examination
Gross examination of skeletal muscle: administration the 45th day, 90 days and drug withdrawal were put to death on the 30th day respectively, observed each internal organs no abnormality seen of internal organs and changed.Each internal organs weightlessness and relative coefficient, each group inspection all in normal range, does not all have the statistics difference, P＞0.05.
Pathologic finding: inspection administration the 90th day and the 30th day convalescent period are respectively organized the rat major organs, there is no the histopathology relevant with administration and change.
(5) anti-interferon detection of antibodies in the blood
Detect the interferon antibody titre blood sampling in 40 days, 90 days, 120 days with the ELISA method.
The result: no matter after continuously vagina administration 90 days and drug withdrawal 30 days be that high dose, low dosage all do not detect interferon antibody.
4. rabbit vagina local excitation test
Vagina effervescent capsule (800,000 IU/ grain) is inserted rabbit vagina, one of every day, a continuous week, after the last administration, put to death rabbit in 24 hours, when dissected cuts vagina, observes longitudinal section and has or not pathological changes such as hyperemia, edema.No matter be blank capsules or contain Drug Capsule to the rabbit vagina mucosa through all administrations, do not see that obviously congested, edema appears in rabbit vagina and secretions increases.
Above-mentioned result of the test shows that recombinanthumaninterferon's vagina effervescent capsule is that preparation is used in the intravaginal of a kind of hypotoxicity, safety.
Clinical research is the result also prove, Interferon Alpha-2b vagina effervescent capsule for treating gynecological cervical erosion total effective rate is 66.2%, and matched group (woman is scorching peaceful) is 43.3%, and other multinomial observation index, as: leucorrhea routine, cleannes, vagina pH value, infusorian, candidiasis inspection, some cases is made human papilloma shape virus (HPV), human herpes simplex vicus II type (HSV-II), Human Cytomegloviru (HCMV) etc., it is scorching peaceful all obviously to be better than the woman, and there are not any stimulation and untoward reaction, more can provide convenience (seeing Table 4) for the patient treats voluntarily.Equal the group controlled trial with Austria and the results are shown in Table 5.
Table 4 Interferon Alfa-2b vagina effervescent capsule clinical observation statistical analysis report (comparing) with the scorching peaceful group of woman
The scorching peaceful group of interferon woman
Project effective percentage effective percentage P value
Example number enabledisable example number enabledisable
(％)??????????????????????(％)
Menstruation improves 213 6 207 2.8 60 1 59 1.7＞0.05
The soreness of waist improves 112 91 21 81.3 37 17 20 45.9＜0.01
Pruritus vulvae 84 79 5 94.0 21 17 4 81.0＞0.05
Contact bleeding 51 47 4 92.2 16 13 3 81.3＞0.05
Leucorrhea character 191 172 19 90.1 52 37 15 71.2＜0.01
Vagina scorching hot 41 40 1 97.6 12 93 75.0＜0.05
Vagina PH 213 167 46 78.4 60 29 31 48.3＜0.01
Leucorrhea cleannes 213 183 30 85.9 60 29 31 48.3＜0.01
Vaginal candida 213 6 207 2.8 60 5 55 8.3＞0.05
Rotten to the corn area 213 141 72 66.2 60 26 34 43.3＜0.01
Table 5 recombinant interferon like product treatment cervical erosion Comparison of therapeutic (with the flat group of Austria)
| The contrast project | Flat group difficult to understand | The Interferon Alpha-2b group | |
| Clinical manifestation | Menstruation changes | Do not add up | 4.6% takes a turn for the better |
| Pruritus vulvae | Improve 88.9% | 94.0% disappears | |
| The leucorrhea character changes | Improve 89.7% | 90.1% improves | |
| Vagina is scorching hot | Do not add up | 97.6% disappears | |
| The urinary system symptom | Improve 1/1 | 11/11 improves | |
| General Symptoms appears in the treatment | 3.2％ | 0％ | |
| Lab testing | Vagina PH value | Do not survey | 78.4% reaches normally |
| The leucorrhea cleannes | Do not survey | 85.9% reaches normally | |
| HPV | Turn out cloudy 100% | Turn out cloudy 100% | |
| HSV-II | Turn out cloudy 100% | Turn out cloudy 100% | |
| CMV | Turn out cloudy 92.6% | Turn out cloudy 100% | |
| Cervical erosion area treatment back total effective rate | 62.6％ | 66.2％ | |
Interferon vagina effervescent capsule of the present invention not only can have the character of disintegrate very fast, molten diffusion and good storage stability when vagina administration; And in interferon capsule process for making of the present invention, causing damage or lose for the interferon protein active component reaches bottom line, can also effectively control the uniformity of drug content in the capsule; Be a kind of reliable in quality, determined curative effect, new forms of interferon vagina administration preparation easy to use.
The specific embodiment
Embodiment 1
1. write out a prescription:
Interferon Alpha-2b 10.5 * 10
9IU
Glucose 1100g
Sorbitol 450g
Malic acid 420g
Sodium bicarbonate 150g
Sodium carbonate 180g
Pregelatinized Starch 350g
Polyvinylpolypyrrolidone 60g
0.5% hydroxypropyl emthylcellulose alcohol-water solution 50g
10% polyethylene pyrrolidone alcohol-water solution 180g
Make 10000 capsules
2. preparation technology
Interferon stock solution is poured in 200 ml phosphate buffers (0.2mol/L pH7.2), mix homogeneously, the sorbitol adjuvant that adds in the prescription mixes, vacuum drying is more than 24 hours under temperature 20 degree, glucose in taking out the back and writing out a prescription equivalent gradually increases progressively and mixes, and makes the particulate fraction that contains the interferon principal agent.
Take by weighing the consumption of malic acid, sodium bicarbonate and sodium carbonate by prescription; put into the boiling granulating machine; the boiling material ventilates; inlet temperature is set at 60 degree; after 10 minutes; by the 0.5% hydroxypropyl emthylcellulose alcoholic solution in the prescription and the mixed solution of 10% polyethylene pyrrolidone alcoholic solution, mist projection granulating is until making the single-size that contains the effervescent composition.
According to prescription, take by weighing through dry pregelatinized Starch and the polyvinylpolypyrrolidone more than 4 hours of baking oven 70 degree, mix with two kinds of above-mentioned uniform particles.
Final hybrid particles is incapsulated, survey Interferon Alpha-2b and tire: 9.02 * 10
5The IU/ grain, moisture content: 1.13%.
Embodiment 2
1. write out a prescription:
Interferon Alpha-2b 10.5 * 10
9IU
Mannitol 1900g
Citric acid 380g
Sodium bicarbonate 230g
Sodium carbonate 110g
Carboxymethyl starch sodium 240g
Polyvinylpolypyrrolidone 30g
12% polyethylene pyrrolidone alcoholic solution 280g
Make 10000 capsules
2. preparation technology
In interferon stock solution and 300 milliliters of citric acid-sodium citrate buffer (0.1mol/LpH6.6), add mannitol again and mix, to handle by example 1 method, temperature remains on subzero 5 vacuum dryings when spending, and makes the powder particle part that contains the interferon principal agent.
Take by weighing the consumption of citric acid, sodium bicarbonate and sodium carbonate by prescription, put into quick mixer granulator, mixed 5 minutes, stir on one side, add polyethylene pyrrolidone alcoholic solution on one side, after finishing, continue to stir 5～7 minutes, until forming single-size.Put into the air-flow baking oven, dry 3～5 hours of 65 degree.
According to prescription, take by weighing through dry carboxymethyl starch sodium and the polyvinylpolypyrrolidone of crossing of baking oven 70 degree, mix with two kinds of above-mentioned uniform particles.
Final hybrid particles is incapsulated, survey Interferon Alpha-2b and tire: 8.01 * 10
5The IU/ grain, moisture content: 1.48%.
Embodiment 3
Interferon Alpha-2b 5 * 10
9IU
Lactose 2150g
Tartaric acid 290g
Calcium carbonate 200g
Sodium carbonate 60g
Carboxymethyl starch sodium 270g
8% polyethylene pyrrolidone alcoholic solution 320g
Make 10000 capsules
2. preparation technology
In the interferonogen feed liquid powdered technology, buffer adopts acetic acid-sodium acetate (0.2mol/LpH7.4), and treatment temperature is controlled at subzero 20 degree, and all the other processing steps are with embodiment 1.The survey Interferon Alpha-2b is tired: 4.12 * 10
5The IU/ grain, moisture content: 1.12%.
Embodiment 4
Interferon Alpha-2b 5 * 10
9IU
Sorbitol 2050g
Boric acid 280g
Sodium bicarbonate 120g
Sodium carbonate 100g
Starch 365g
10% polyethylene pyrrolidone alcoholic solution 340g
Make 10000 capsules
2. preparation technology
The interferonogen feed liquid is controlled at subzero 10 degree with treatment temperature with borate buffer (0.1mol/L pH6.2) dilution in the powdered technology, and all the other processing steps are with embodiment 2.The survey Interferon Alpha-2b is tired: 4.05 * 10
5The IU/ grain, moisture content: 1.13%.
Claims (10)
1, a kind of interferon vagina effervescent capsule is characterized in that the percentage by weight of this effervescent capsule prescription consists of:
The amounts of components scope
Interferon 4 * 10
9IU～11 * 10
9IU
Water soluble adjuvant 16%～84%
Gas-producing disintegrant 2%～67%
Complementary disintegrating agent 0～20%
Binding agent is an amount of
Make 10000 capsules.
2, interferon vagina effervescent capsule according to claim 1 is characterized in that wherein said interferon is natural or Interferon Alfa-2b and analog thereof.
3, interferon vagina effervescent capsule according to claim 1 is characterized in that wherein said water soluble adjuvant is selected from one or more mixture of lactose, mannitol, glucose or sorbitol.
4, interferon vagina effervescent capsule according to claim 1 is characterized in that wherein said gas-producing disintegrant is selected from carbonate and acid.
5, interferon vagina effervescent capsule according to claim 4 is characterized in that wherein said carbonate comprises sodium carbonate, sodium bicarbonate, calcium carbonate, potassium carbonate or potassium bicarbonate; Acid comprises malic acid, citric acid, tartaric acid, alginic acid or boric acid.
6, interferon vagina effervescent capsule according to claim 1 is characterized in that wherein said binding agent is selected from polyethylene pyrrolidone, hydroxypropyl emthylcellulose or ethanol.
7, the capsular preparation method of interferon vagina effervescent according to claim 1 is characterized in that the capsular preparation of this effervescent comprises the following steps:
(1) preparation interferon particles
The dissolved dilution in solvent medium with interferon or its analog, add the part water soluble adjuvant, behind the mix homogeneously, vacuum drying, baking temperature be controlled at subzero 30 ℃ to 25 ℃ of scopes of room temperature, make the solids that contains principal agent, and then with the principle of equivalent incremental method, append the part water soluble adjuvant, after amplifying dilution the interferon powder particle, detect the granule water content and the uniformity and answer requirement up to specification, and measure interferon content;
(2) preparation effervescent particulate
With the gas-producing disintegrant mix homogeneously of carbonate and acid, add an amount of binding agent and carry out mixing granulation, make the granules of accessories particle size range of effervescent disintegrate account for 1%-30% less than 75 μ m, account for 5%-50% greater than 300 μ m;
(3) granule that step (1) and (2) are made adds complementary disintegrating agent, and mix homogeneously, the moisture content of total mixture are controlled in 0.2～5.0% scope, and filled capsules promptly.
8, the capsular preparation method of interferon vagina effervescent according to claim 7 is characterized in that wherein said solvent comprises purified water or the pH value buffer solution between 3.0-8.0.
9, the capsular preparation method of interferon vagina effervescent according to claim 8 is characterized in that wherein said buffer solution is selected from borate buffer solution, phosphate buffer solution, citric acid solution or acetate buffer.
10, the application of interferon vagina effervescent capsule according to claim 1 in preparation treatment cervicitis, cervical erosion medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03141819 CN1281272C (en) | 2003-07-25 | 2003-07-25 | Interferon effervescence capsule for vagina used and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03141819 CN1281272C (en) | 2003-07-25 | 2003-07-25 | Interferon effervescence capsule for vagina used and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1569224A true CN1569224A (en) | 2005-01-26 |
| CN1281272C CN1281272C (en) | 2006-10-25 |
Family
ID=34471066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03141819 Expired - Lifetime CN1281272C (en) | 2003-07-25 | 2003-07-25 | Interferon effervescence capsule for vagina used and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1281272C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102188405A (en) * | 2011-05-10 | 2011-09-21 | 田振坤 | New cavity administration preparation formulation |
| CN105326807A (en) * | 2015-11-20 | 2016-02-17 | 上海华新生物高技术有限公司 | Interferon vaginal effervescent capsule and preparation method thereof |
-
2003
- 2003-07-25 CN CN 03141819 patent/CN1281272C/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102188405A (en) * | 2011-05-10 | 2011-09-21 | 田振坤 | New cavity administration preparation formulation |
| CN105326807A (en) * | 2015-11-20 | 2016-02-17 | 上海华新生物高技术有限公司 | Interferon vaginal effervescent capsule and preparation method thereof |
| WO2017084612A1 (en) * | 2015-11-20 | 2017-05-26 | 上海华新生物高技术有限公司 | Interferon vaginal effervescent capsules and preparation method therefor |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1281272C (en) | 2006-10-25 |
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