CN1227124A - Beta interferon lozenge and its preparing method - Google Patents
Beta interferon lozenge and its preparing method Download PDFInfo
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Abstract
Beta interferon lozenge contains low-dosage beta interferon as effective component and medically acceptable supplementary material. The present invention also provides the lozenge preparing process at low and normal temperature conditions. The lozenge is suitable for the treatment of viral infection and tumor, and has the advantages of obvious curative effect, low toxicity, stable performance, etc.
Description
The present invention relates to the medical biotechnology field, relate in particular to beta interferon lozenge and manufacture method thereof.
Interferon is the naturally occurring protein of a class, is divided into three classes: interferon-alpha, interferon-and IFN-.They are cytokines of finding the earliest, have biological activitys such as antiviral, antitumor and immunomodulating.
Interferon-(IFN-β) mainly suppresses the growth of virus by duplicating of viral interference RNA or DNA, and can significantly strengthen the killing activity of NK cell, and the expression enhanced CT L by promoting the mhc class i molecule is to the identification and the lethal effect of virus infected cell.Clinically, IFN-β has been used to treat multiple disease, especially viral infection, for example viral infection such as hepatitis B, hepatitis C, HBV, HPV, HIV, HSV is all had curative effect preferably.In addition, IFN-β also has certain antitumor action, for example non-small cell type pulmonary carcinoma, breast carcinoma, laryngeal carcinoma, colon cancer and renal carcinoma etc. is all had certain curative effect.
At present, the route of administration that clinically interferon and interleukin II is used for the treatment of viral infection and tumor is mainly two kinds of intramuscular injection and intravenous injections, though heavy dose of muscle or intravenous curative effect are sure, exists following shortcoming.Dosage is big, the course of treatment is long.For example, the therapeutic dose of interferon-is generally in that 3,000,000 IU/ people/more than the sky, the administration cycle was generally 1 to 12 months; The therapeutic dose of interferon-alpha is generally 300 to 5,000,000 IU/ people/skies, and the administration cycle was generally 1 to 6 months; The therapeutic dose of interleukin II is generally 10 to 500,000 IU/ people/skies, and the administration cycle was generally 0.5 to 1 month.Because human body is low to the toleration of injection of interferon and interleukin II, a lot of patients have produced serious adverse effects because of large bolus injection, often therefore are forced to end to use injection-type interferon and interleukin II.In addition, injection-type interferon and interleukin II cost an arm and a leg, if use a course of treatment 1 to 12 months, only drug expenditure is just up to units up to ten thousand, and for now, the individual often is difficult to bear.Owing to above reason, many patients are abandoning cure and affect the state of an illness adversely midway often.
So all the time, people need low, the convenient drug administration of a kind of dosage, and bring the interferon novel dosage form of advantages such as inexpensive and side effect is low thus.
Find after deliberation, interferon-alpha can be in conjunction with cell surface receptor through low dose oral, the Fc acceptor quantity of IgG on the expression of enhancing MHC, increase mononuclear cell and the macrophage, increase the cell-mediated dissolution of NK, cause and enlarge serial immunoregulation effect thus, finally reach a kind of virus replication and and then the viral effect of elimination.Existing report mouthful with the low dosage interferon-alpha to hepatitis B have tangible curative effect (the Bocci V. " clinical pharmacokinetics " (Clin pharmacokinet.) 21 (6): 411-417,1991; Paulesu L. etc., " International Pharmaceutical magazine " be 46:199-202 (Int.J.Pharm.), and 1988).Based on above discovery, people have developed the peroral dosage form of interferon-alpha.For example, Australian Namawa cell beta interferon lozenge having been arranged, is to be the source with the lymphoma cell, and the natural interferon-alpha through Sendai virus mutation produces has tens kinds of hypotypes; And disclosed Chinese patent application 95101212.9 and Chinese patent application 95111433.6, wherein all having related to is the interferon lozenge and the preparation method of Main Ingredients and Appearance with the interferon-alpha.
But, as biological activity in these interferon peroral dosage forms all is interferon-alpha, and be mixed and made into buccal tablet with the interferon-of low dosage as active ingredient and proper supplementary material, and the purposes in viral infection or oncotherapy yet there are no report so far.So people still need the interferon-of peroral dosage form, in its unique pharmacologically active and clinical efficacy of performance, make it more possess new peroral dosage form convenient drug administration, cheap, advantage such as side effect is little.
At present, for the interferon-oral administration sure report (NelsonP.A. etc., " mouthful with interferon-in the effect that causes aspect the immunne response " are 778:145-155 (Ann.N.Y.Acad.Sci.), 1996) can induce immune response have been arranged.We also find in research, interferon-can be carried out oral to contain tablet form, utilize the local disintegrate of buccal tablet in the oral cavity, oral transmucosal absorbs than low dosage the time, activate local immune system, and further amplify this immune activation effect, thereby performance antitumor, infection and immunoregulatory effect.In addition, we find that also when interferon-and interferon-alpha or interleukin II share, effect had significant cooperative effect to immune activation.
Therefore, one of purpose of the present invention is to provide a kind of beta interferon lozenge, fills up no this blank of oral beta interferon lozenge in the prior art.Specifically, when obtaining and/or strengthening the unique curative effect of interferon-, overcome interferon high dose injection course of treatment long, toxicity is big, patient's toleration difference and shortcoming such as cost an arm and a leg.
Another object of the present invention is to provide the preparation method of the above beta interferon lozenge.Make that interferon-inactivation in preparation process is few, and behind the chamber, import, can slowly discharge.
In order to reach described purpose, the invention provides a kind of beta interferon lozenge, it comprise as the interferon-of active ingredient and pharmaceutically the approval adjuvant, make the buccal tablet dosage form.The content of described interferon-is every 1,000IU to 10, and 000IU, 2000IU to 5000IU is better.
Interferon-as active ingredient of the present invention refers to any reorganization or natural human interferon-.The commercial goods of Switzerland Serono company and U.S. Berlex company for example.
As the pharmaceutically adjuvant of approval of the present invention, be selected from for example human albumin, Polyethylene Glycol, lactose, glucose, starch, mannitol, bovine serum albumin, magnesium stearate and dextrin.Be the commercial goods.
In the present invention preferably in the embodiment, we find to add interferon-alpha and interleukin II as the potentiation composition in described beta interferon lozenge.When they share with interferon-respectively, has tangible synergy.
Being used for interferon-alpha of the present invention can be any natural or recombinant alpha interferon.The for example natural interferon-alpha of Shanghai Vaccine and Serum Institute and Sansheng Medicinal Industry Co., Ltd., Shenyang, and the recombinant alpha interferon of Shenzhen Kexing Biological Products Co., Ltd.Its content is every 100IU to 1,000IU; 100IU to 500IU is better.Interleukin II can be any natural or the reorganization interleukin II, its content is every 1,000IU to 10,000IU; 2000IU to 5000IU is better.
The dosage form that the present invention adopts is a sublingual lozenge.
The present invention also provides a kind of method for preparing the interferon-sublingual lozenge, and this method comprises:
The adjuvant of aseptic interferon-with pharmaceutically approval mixed, and lyophilization becomes lyophilized powder;
The adjuvant of pharmaceutically approval is mixed, and through sieving, drying is prepared into blank granule;
Sampling multiple proportions mixing method is fully mixed blank granule with lyophilized powder;
At low temperature direct compression to the normal temperature condition.
The present invention also provides the another kind of method for preparing the interferon-sublingual lozenge, and this method comprises:
The adjuvant of pharmaceutically approval is mixed, and through sieving, drying is prepared into blank granule;
Aseptic interferon-and the adjuvant of pharmaceutically approving are prepared into solution;
Described solution evenly is sprayed on the blank granule with nebulization;
Oven dry then;
At low temperature direct compression to the normal temperature condition.
Preferably in one of embodiment, the invention provides a kind of method for preparing the interferon-sublingual lozenge in the present invention, this method comprises:
With aseptic interferon-, aseptic interferon-alpha or interleukin II mix with the adjuvant of pharmaceutically approval, and lyophilization becomes lyophilized powder;
The adjuvant of pharmaceutically approval is mixed, and through sieving, drying is prepared into blank granule;
Sampling multiple proportions mixing method is fully mixed blank granule with lyophilized powder;
At low temperature direct compression to the normal temperature condition.
The present invention another preferably in the embodiment, the invention provides a kind of method for preparing the interferon-sublingual lozenge, this method comprises:
The adjuvant of pharmaceutically approval is mixed, and through sieving, drying is prepared into blank granule;
With aseptic interferon-, the adjuvant of aseptic interferon-alpha or interleukin II and pharmaceutically approval is prepared into solution;
Described solution evenly is sprayed on the blank granule with nebulization;
Oven dry then;
At low temperature direct compression to the normal temperature condition.
The present invention is the buccal tablet that active ingredient is made with the interferon-, because containing tablet form oral transmucosal after the local disintegrate in oral cavity absorbs, just can activate local immune system than low dosage, and further amplify this immune activation effect, so the present invention just can obtain antitumor, viral infection resisting and the immunoregulatory effect of interferon-uniqueness when low dosage.In addition because the unique separately pharmacological action of interferon-alpha and interleukin II, when they respectively with interferon-with when share, the immune activation effect is also had significant cooperative effect, strengthened curative effect greatly.So, of the present invention have evident in efficacy, toxicity is low, convenient oral, low price, etc. advantage.
And because the adjuvant that the present invention selects for use, for example albumin, mannitol, Polyethylene Glycol etc. have static stabilization, and make the form of buccal tablet, thereby make buccal tablet of the present invention have good stability, advantage such as can in the oral cavity, slowly discharge in addition, owing to adopted the process conditions of low temperature to room temperature, the present invention also to have the few advantage of interferon-inactivation in preparation process.
Further describe the present invention below with reference to embodiment.Advantage of the present invention and beneficial effect also will become apparent thus.
Embodiment 1
Get aseptic interferon-(Switzerland Serono company) 3,600 ten thousand IU (loss of activity of interferon is 20% behind the tabletting), mix with 100g mannitol (Changzheng Pharmaceutical Factory, Shanghai) (20% solution) and 20g human albumin (the albumin injection that Shanghai Vaccine and Serum Institute produces), place stainless steel disc, lyophilization becomes dry powder.
Get magnesium stearate (Shanghai pharmaceutic adjuvant factory) 100g, dextrin (Shanghai pharmaceutic adjuvant factory) 18g mix homogeneously with starch (North China Pharmaceutical Factory) 400g mix homogeneously, is prepared into soft material then thus.The soft material that will wet is crossed 20 purposes sieve and is prepared into granule.At 60 ℃ baking ovens (Hereaus company) inner drying granule, be 5-10% until water content.Be prepared into blank granule thus.
The interferon-lyophilized powder is fully mixed with the blank granule of equivalent.This mixture is fully mixed with remaining blank granule again, guarantee that thus interferon-content in mixture is even.
In advance with the thermoregulation of tablet machine (available from German Ke Lian company) at-4-20 ℃, and guarantee that in operating process temperature is no more than 20 ℃, becomes 10,000 with the mixture tabletting.
Embodiment 2
Get mannitol (Changzheng Pharmaceutical Factory, Shanghai) 100g, magnesium stearate (Shanghai pharmaceutic adjuvant factory) 80g and dextrin (Shanghai pharmaceutic adjuvant factory) 150g mix homogeneously are prepared into soft material with starch (North China Pharmaceutical Factory) 450g uniform mixing then.Wet soft material sieves through 20 purposes sieve and is prepared into granule.At 60 ℃ baking ovens (Hereaus company) inner drying granule, be 5-10% until water content.Be prepared into blank granule thus.
Get aseptic interferon-(Switzerland Serono company) 3600IU (loss of activity of interferon is 20% behind the tabletting) and be uniformly mixed into solution with aseptic albumin (20g) (the albumin injection that Shanghai Vaccine and Serum Institute produces).
Interferon-solution evenly is sprayed on the blank granule (spraying machine available from German Ke Lian company) with nebulization.Then 37 ℃ of oven dry 3-5 hour.
In advance with the thermoregulation of tablet machine (available from German Ke Lian company) at-4-20 ℃, and guarantee that in operating process temperature is no more than 20 ℃, becomes 10,000 with the mixture tabletting.
Embodiment 3
Get aseptic interferon-(Switzerland Serono company) (2400IU) and natural interferon-alpha (Shanghai Vaccine and Serum Institute) (240IU) (loss of activity of interferon is 20% behind the tabletting), mix with 100g mannitol (Changzheng Pharmaceutical Factory, Shanghai) (20% solution) and 20g human albumin (the albumin injection that Shanghai Vaccine and Serum Institute produces), place stainless steel disc, lyophilization becomes dry powder.
Get magnesium stearate (Shanghai pharmaceutic adjuvant factory) 150g, dextrin (Shanghai pharmaceutic adjuvant factory) 100g mix homogeneously with starch (North China Pharmaceutical Factory) 400g mix homogeneously, is prepared into soft material then thus.The soft material that will wet is crossed 20 purposes sieve and is prepared into granule.At 60 ℃ baking ovens (Hereaus company) inner drying granule, be 5-10% until water content.Be prepared into blank granule thus.
The interferon freeze-drying powder is fully mixed with the blank granule of equivalent.This mixture is fully mixed with remaining blank granule again, guarantee that thus interferon content in mixture is even.
In advance with the thermoregulation of tablet machine (available from German Ke Lian company) at-4-20 ℃, and guarantee that in operating process temperature is no more than 20 ℃, becomes 10,000 with the mixture tabletting.
Embodiment 4
Get mannitol (Changzheng Pharmaceutical Factory, Shanghai) 100g, magnesium stearate (Shanghai pharmaceutic adjuvant factory) 100g and dextrin (Shanghai pharmaceutic adjuvant factory) 140g mix homogeneously are prepared into soft material with starch (North China Pharmaceutical Factory) 400g uniform mixing then.Wet soft material sieves through 20 purposes sieve and is prepared into granule.At 60 ℃ baking ovens (Hereaus company) inner drying granule, be 5-10% until water content.Be prepared into blank granule thus.
Get aseptic interferon-(Switzerland Serono company) 2,400 ten thousand IU and natural interferon-alpha (Shanghai Vaccine and Serum Institute) 2,400,000 IU (loss of activity of interferon is 20% behind the tabletting) and be uniformly mixed into solution with the aseptic albumin of 20g (Shanghai Vaccine and Serum Institute).
Interferon solution evenly is sprayed on the blank granule (spraying machine available from German Ke Lian company) with nebulization.Then 37 ℃ of oven dry 3-5 hour.
In advance with the thermoregulation of tablet machine (available from German Ke Lian company) at-4-20 ℃, and guarantee that in operating process temperature is no more than 20 ℃, becomes 10,000 with the mixture tabletting.
Embodiment 5
According to embodiment 1 or 2 described methods, replace mannitol with PEG2000 (Gao Nan chemical plant, Chuansha, Shanghai), and add lactose, according to following formulation beta interferon lozenge, totally 1000.
Form content
Interferon-(Switzerland Serono company) 1,000,000 IU
Human albumin (Shanghai Vaccine and Serum Institute) 2g
PEG2000 (Gao Nan chemical plant, Chuansha, Shanghai) 5g
Starch (North China Pharmaceutical Factory) 45g
Magnesium stearate (Shanghai pharmaceutic adjuvant factory) 8g
Lactose (Xi'an pharmaceutical factory) 5g
Dextrin (Shanghai pharmaceutic adjuvant factory) 15g
Embodiment 6
According to embodiment 1 or 2 described methods, use bovine serum albumin to replace the human albumin, and add lactose, according to following formulation beta interferon lozenge, totally 1000.
Form content
Interferon-(Switzerland Serono company) 1,000 ten thousand IU
Bovine serum albumin (biological reagent shop, Shanghai) 1g
Lactose (Xi'an pharmaceutical factory) 11g
Mannitol (Changzheng Pharmaceutical Factory, Shanghai) 10g
Starch (North China Pharmaceutical Factory) 45g
Magnesium stearate (Shanghai pharmaceutic adjuvant factory) 5g
Dextrin (Shanghai pharmaceutic adjuvant factory) 18g
Embodiment 7
According to embodiment 1 or 2 described methods, according to following formulation beta interferon lozenge, totally 1000.
Form content
Interferon-(Switzerland Serono company) 2,000,000 IU
Human albumin (Shanghai Vaccine and Serum Institute) 2g
Mannitol (Changzheng Pharmaceutical Factory, Shanghai) 10g
Starch (North China Pharmaceutical Factory) 50g
Magnesium stearate (Fructus Vitis viniferae sugar refinery, Shanghai) 10g
Dextrin (Fructus Vitis viniferae sugar refinery, Shanghai) 18g
Embodiment 8
According to embodiment 3 or 4 described methods, use bovine serum albumin to replace the human albumin, do not use starch, use lactose and glucose, according to following formulation beta interferon lozenge, totally 1000.
Form content
Interferon-(Switzerland Serono company) 1,000,000 IU
(the Shanghai biological product are studied 100,000 IU to natural interferon-alpha
The institute)
Sanguis Bovis seu Bubali albumin (Weihui City, Shanghai chemical reagent work) 4g
Mannitol (Changzheng Pharmaceutical Factory, Shanghai) 20g
Lactose (inland river, Sichuan pharmaceutical factory) 10g
Glucose (inland river, Sichuan pharmaceutical factory) 25g
Magnesium stearate (Fructus Vitis viniferae sugar refinery, Shanghai) 5g
Dextrin (Fructus Vitis viniferae sugar refinery, Shanghai) 16g
Embodiment 9
According to embodiment 3 or 4 described methods, use recombinant alpha interferon to replace natural interferon-alpha, and add glucose, according to following formulation beta interferon lozenge, totally 1000.
Form content
Interferon-(Switzerland Serono company) 1,000 ten thousand IU
Recombinant alpha interferon (Shenzhen Kexing Biological Products Co., Ltd) 1,000,000 IU
Human albumin (Shanghai Vaccine and Serum Institute) 5g
Mannitol (Changzheng Pharmaceutical Factory, Shanghai) 10g
Glucose (inland river, Sichuan pharmaceutical factory) 5g
Starch (North China Pharmaceutical Factory) 5g
Magnesium stearate (Fructus Vitis viniferae sugar refinery, Shanghai) 8g
Dextrin (Fructus Vitis viniferae sugar refinery, Shanghai) 12g
Embodiment 10
According to embodiment 3 or 4 described methods, and add glucose, according to following formulation beta interferon lozenge, totally 1000.
Form content
Interferon-(Switzerland Serono company) 2,000,000 IU
(the Shanghai biological product are studied 200,000 IU to natural interferon-alpha
The institute)
Human albumin (Shanghai Vaccine and Serum Institute) 4g
Mannitol (Changzheng Pharmaceutical Factory, Shanghai) 10g
Glucose (Xi'an pharmaceutical factory) 5g
Starch (Yadong, Shanghai Pharma Inc.) 5g
Magnesium stearate (Fructus Vitis viniferae sugar refinery, Shanghai) 8g
Dextrin (Fructus Vitis viniferae sugar refinery, Shanghai) 12g
Embodiment 11
According to embodiment 3 or 4 described methods, replace interferon-alpha with interleukin II, according to following formulation beta interferon lozenge, totally 1000.
Form content
Interferon-(Switzerland Serono company) 1,000,000 IU
Interleukin II (Shenyang three lives Pharma Inc.) 1,000,000 IU
Human albumin (Shanghai Vaccine and Serum Institute) 3g
Mannitol (Changzheng Pharmaceutical Factory, Shanghai) 15g
Starch (Yadong, Shanghai Pharma Inc.) 50g
Magnesium stearate (Fructus Vitis viniferae sugar refinery, Shanghai) 10g
Dextrin (Fructus Vitis viniferae sugar refinery, Shanghai) 17g
Embodiment 12
According to embodiment 3 or 4 described methods, replace interferon-alpha with interleukin II, do not use starch, and add lactose, according to following formulation beta interferon lozenge, totally 1000.
Form content
Interferon-(Switzerland Serono company) 1,000 ten thousand IU
Interleukin II (Shenyang three lives Pharma Inc.) 1,000 ten thousand IU
Human albumin (Shanghai Vaccine and Serum Institute) 3g
Mannitol (Changzheng Pharmaceutical Factory, Shanghai) 15g
Lactose (Xi'an pharmaceutical factory) 55g
Magnesium stearate (Fructus Vitis viniferae sugar refinery, Shanghai) 10g
Dextrin (Fructus Vitis viniferae sugar refinery, Shanghai) 12g
Embodiment 13
According to embodiment 3 or 4 described methods, replace interferon-alpha with interleukin II, according to following formulation beta interferon lozenge, totally 1000.
Form content
Interferon-(Switzerland Serono company) 2,000,000 IU
Interleukin II (Shenyang three lives Pharma Inc.) 2,000,000 IU
Human albumin (Shanghai Vaccine and Serum Institute) 5g
Mannitol (Changzheng Pharmaceutical Factory, Shanghai) 15g
Starch (Yadong, Shanghai Pharma Inc.) 45g
Magnesium stearate (Fructus Vitis viniferae sugar refinery, Shanghai) 10g
Dextrin (Fructus Vitis viniferae sugar refinery, Shanghai) 15g
Embodiment 14
According to embodiment 3 or 4 described methods, replace interferon-alpha with interleukin II, replace the human serum albumin with bovine serum albumin, replace mannitol with Polyethylene Glycol (PEG2000), according to following formulation beta interferon lozenge, totally 1000.
Form content
Interferon-(Switzerland Serono company) 3,000,000 IU
Interleukin II (Shenyang three lives Pharma Inc.) 5,000,000 IU
Sanguis Bovis seu Bubali albumin (Weihui City, Shanghai chemical reagent work) 3g
PEG2000 (Gao Nan chemical plant, Chuansha, Shanghai) 10g
Starch (Yadong, Shanghai Pharma Inc.) 50g
Magnesium stearate (Fructus Vitis viniferae sugar refinery, Shanghai) 10g
Dextrin (Fructus Vitis viniferae sugar refinery, Shanghai) 22g
The test implementation example
Test 1
Carry out acute toxicity testing with healthy Kunming mouse (providing),, give beta interferon lozenge of the present invention through irritating stomach 20 mices with Cmax, maximum volume 0.5ml by the The 2nd Army Medical College Experimental Animal Center.Observed 7 days continuously, do not find any toxic and side effects.Experimental result shows that the maximum tolerated dose of oral beta interferon lozenge is a human dosage, promptly 50000 of 2000IU/ day times.
Test 2
Get a slice buccal tablet of the present invention and pulverize, mix in the RPMI-1640 culture medium of adding 5-10ml and stir, spend the night in 4 ℃ of placements then.Use the membrane filtration of 50um then, collect filtrate.Use conventional method, promptly the WISH method is measured interferon content wherein.After measured, wherein the content of interferon-is 100 ± 10% of labelled amount.
Buccal tablet of the present invention was placed 2 years under 4 to 10 ℃ of environment, measured, the activity of interferon-, interferon-alpha and interleukin II, active no significant change through the WISH method.
Clinical experiment
Experiment 1
Certain patient, the male 50 years old, is diagnosed as hepatitis B, medical history 7 years.After the patient rises morning every day, sublingual administration a slice embodiment of the invention 7 described beta interferon lozenges (interferon-content wherein is 2000IU), buccal 10 to 30 minutes.Through the treatment of half a year, it is normal that the ALT level is recovered, and HBeAg turns out cloudy.
Experiment 2
Certain patient, the women 33 years old, is diagnosed as hepatitis B, medical history 3 years.Independent oral administration of alpha interferon tablet is once taken half a year and invalid.After the patient rises morning every day, sublingual administration a slice embodiment of the invention 10 described beta interferon lozenges (interferon-content wherein is 2000IU, and interferon-alpha content is 200IU), buccal 10 to 30 minutes.Treatment through 1 year, ALT level recover normal, and HBeAg turns out cloudy
Comparing embodiment
40 of nude mices are divided into 5 groups at random: A organizes oral normal saline, in contrast; B organizes oral interferon-100IU/kg; C organizes oral interferon-100IU/kg and 200IU/kg interleukin II; D organizes oral interferon-100IU/kg and interferon-alpha 10IU/kg; E group injection interferon-100IU/kg; F group injection interferon-10,000IU/kg.Successive administration detects nude mice cell NK activity after 1 week.The result is as follows:
The active % of grouping drug administration approach dosage NK
The A normal saline is oral--and 7.9 ± 2.8%
The oral 100IU/kg 19.9 ± 3.3% of B interferon-
*#
The oral 100IU/kg 22.8 ± 6.1% of C interferon-
*
Interleukin
2200IU/kg
The oral 100IU/kg 28.6 ± 6.5% of D interferon-
*
Interferon-alpha 10IU/kg
E interferon-injection 100IU/kg 8.5 ± 3.0%
F interferon-injection 10,000IU/kg 17.7 ± 1.8%
*
*Compare P＜0.01 with A
# and E compare, P＜0.01
Owing to there is species variation, human beta interferon is invalid to mice, so come the effect of appraiser's interferon without mice.But owing to lack the T cell in the nude mouse, so the 1NK activity is as immune indexes.Experimental result shows, interferon-is single with, interferon-and interleukin II share or interferon-and interferon-alpha are share the effect that all has the booster immunization function, and has synergism when share.In addition, compare with injection type, oral with the dosage interferon-to the inducing action of immunologic function apparently higher than injection, its effect is suitable with 100 times injected dose.
Claims (11)
1. beta interferon lozenge, it is characterized in that, the adjuvant that it comprises interferon-and pharmaceutically approves, the content of described interferon-is every 1,000IU to 10,000IU, described adjuvant is selected from human albumin, bovine serum albumin, Polyethylene Glycol, mannitol, lactose, glucose, starch, magnesium stearate and dextrin.
2. beta interferon lozenge according to claim 1 is characterized in that, the content of described interferon-is every 2000IU to 5000IU.
3. beta interferon lozenge according to claim 1 is characterized in that, the content of described interferon-is every 2000IU.
4. beta interferon lozenge according to claim 1 is characterized in that it also comprises interferon-alpha, and wherein the content of interferon-alpha is every 100IU to 1,000IU.
5. beta interferon lozenge according to claim 4 is characterized in that it also comprises 0 interferon-alpha, and wherein the content of interferon-alpha is every 100IU to 500IU.
6. beta interferon lozenge according to claim 4 is characterized in that, the content of described interferon-is every 2000IU, and the content of interferon-alpha is every 200IU.
7. beta interferon lozenge according to claim 1 is characterized in that it also comprises interleukin II, and wherein the content of interleukin II is every 1,000IU to 10,000IU.
8. beta interferon lozenge according to claim 7 is characterized in that it also comprises interleukin II, and wherein the content of interleukin II is every 2,000IU to 5,000IU.
9. beta interferon lozenge according to claim 7 is characterized in that, the content of described interferon-is every 2000IU, and the content of interleukin II is every 2000IU.
10. method for preparing beta interferon lozenge as claimed in claim 1 is characterized in that it comprises:
The adjuvant of aseptic interferon-with pharmaceutically approval mixed, and lyophilization becomes lyophilized powder;
The adjuvant of pharmaceutically approval is mixed, and through sieving, drying is prepared into blank granule;
Sampling multiple proportions mixing method is fully mixed blank granule with lyophilized powder;
At low temperature direct compression to the normal temperature condition.
11. a method for preparing interferon lozenge as claimed in claim 1 is characterized in that it comprises:
The adjuvant of pharmaceutically approval is mixed, and through sieving, drying is prepared into blank granule;
Aseptic interferon-and the adjuvant of pharmaceutically approving are prepared into solution;
Described solution evenly is sprayed on the blank granule with nebulization;
Oven dry then;
At low temperature direct compression to the normal temperature condition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 98105383 CN1227124A (en) | 1998-02-25 | 1998-02-25 | Beta interferon lozenge and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 98105383 CN1227124A (en) | 1998-02-25 | 1998-02-25 | Beta interferon lozenge and its preparing method |
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| Publication Number | Publication Date |
|---|---|
| CN1227124A true CN1227124A (en) | 1999-09-01 |
Family
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| CN 98105383 Pending CN1227124A (en) | 1998-02-25 | 1998-02-25 | Beta interferon lozenge and its preparing method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100345590C (en) * | 2003-08-14 | 2007-10-31 | 福建广生堂药业有限公司 | Lozenge containing liver cell growth promoting agent and interferon |
-
1998
- 1998-02-25 CN CN 98105383 patent/CN1227124A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100345590C (en) * | 2003-08-14 | 2007-10-31 | 福建广生堂药业有限公司 | Lozenge containing liver cell growth promoting agent and interferon |
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