CN1759887A - Mucous membrane absorption ingestion type medicinal composition for drawing out interferon, and preparation - Google Patents
Mucous membrane absorption ingestion type medicinal composition for drawing out interferon, and preparation Download PDFInfo
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Abstract
A mucosa absorption type medicinal composition for inducing interferon contains the polymyocell or its derivative and one or more of the pharmacologically acceptable salts and the polycationic compound and one or more of the pharmacologically acceptable salts. Its preparation in the form of solution, aerosol, spray, or powder for inducing the immune system to generate interferon is also disclosed.
Description
Technical field
The dosage form that the present invention relates to a kind of Pharmaceutical composition of inducement interferon and adopt this Pharmaceutical composition, more particularly, the present invention relates to a kind of can be well by mucous membrane tissue absorbed and absorbed, be used for inducement interferon Pharmaceutical composition and dosage form thereof.
Background technology
Interferon (IFN) has antiproliferative effect and antivirus action.Double stranded RNA can be used as the inducer (J.Reticuloendothelial Society, 23,299,1978) of the interferon of models such as α, β, the γ of people and animal.Induce the function that IFN produced and induced NK cell (NK) cell because natural double stranded RNA and synthetic double stranded RNA all have, so they all can be used as vaccine.Representative double stranded RNA has polyinosini (PolyIC), polyinosini urine and gathers gland urine.For example, disclosed a kind of synthetic double stranded RNA (being polyinosini) that exists with the composite form of poly ribose inosinic acid and poly ribose cytidylic acid in the United States Patent (USP) 3666646.Again for example, U.S. Pat 4024222 and US4130641 disclose a class polyinosini and have mixed the ribosyl skeleton of unpaired base (uracil or guanine) and the polyinosini mismatch analog that forms along poly ribose cytidylic acid (PolyC) or poly ribose inosinic acid (PolyI) chain.Wherein, polyinosini urine is exactly that polyinosini mixes unpaired uracil along poly ribose cytidylic acid (PolyC) chain and forms.Have experiment to show, compare with polyinosini, the consumption of polyinosini urine is few, but more effective and side effect is less.U.S. Pat 6080726 has proposed the Therapeutic Method of independent use mismatch polyinosini urine (polyI.polyr (C12.U)) nose administration treatment viral disease.The inducer of interferon such as polyinosini (IFN) molecule is mainly used in treatment viral keratitis, herpes simplex, mumps clinically, prevents respiratory tract infection, also can be used for the auxiliary treatment of hepatitis, tumor.Use polyinosini and derivant thereof at present clinically normally by intravenously administrable, but this route of administration can cause that the patient generates heat etc. side effect, thereby the use of this class medicine has been caused restriction.For example, to behind patient's intravenous injection polyinosini injection, the patient often produces heating.
People further investigate over against the vaccine of per mucous membrane immunity, and have obtained bigger progress (Clinical Applied Immunology Reviews, 3,183,2003).The up breathing of mammalian hosts and gastrointestinal region are evolved and have been formed secondary lymphoid tissue, and this helps antigenic picked-up, processes and presents, thereby produce mucosal immune response.Gastrointestinal mucosa induction position comprises Peyer patches (Peyer ' s patches), caecum (vermiform appendix) and solitary lymph follicle, and they constitute gastrointestinal dependency lymphoreticular tissue (GALT) together; Bronchus dependency lymphoreticular tissue (BALT) in the air flue can be defendd the antigen of intranasal/suction, and each kind differences of its evolution degree is bigger.Family exempts from, rat and Cavia porcellus BALT grow significantly, and people and mice intranasal/the main induction tissue of antigen that sucks may be palatine tonsil adenoid vegetation and nasopharynx tonsil, their common lymphoid tissue waldeyer's rings (Waldeyeming) that forms now are commonly referred to as nasopharynx dependency lymphoreticular tissue (NALT).Traditional parenteral vaccination is though the systemic disease that can well prevent the pathogen invasion and attack to cause is invalid to mucosa infection.Reason is that the parenteral vaccination can not be reacted at mucosa position induction of immunity.Little fold cell (M cell) in the mucosa dependency lymphoreticular tissue (MALT) is taken in antigen and is striden cell passage and causes complete antigen to enter following lymphoid tissue, these antigens comprise pathogen, natural or synthetic double stranded RNA, after in MALT, contacting antigen first, the mucosa lymphocyte leaves the induction position, gets back to mucosa effect tissue.This approach can be induced the immunity at a plurality of mucosas position simultaneously, is called common mucosa-immune system (CMIS).Result of study shows: have only a mucosa inductive site that is made of the epithelium lymph follicle is carried out vaccination, effectively the immunoreation of the common mucosa of stimulation system.Its reason is that the activated lymphocyte in mucosa position is optionally gone back to the nest to the mucosa lymphoid tissue, makes mucosa lymphocyte and system's lymphocyte be in half isolation.There are some researches show that also owing to there is common mucosa system, the immunostimulation at different mucosas position except that immunoreation is brought out in the part, also has immunoreactive generation (Immunol Res16,187,1997) at other position.Nearest research is more found: the nasal mucosa immunity is inducible system and the partial immunoreation of many places mucosa (J Immunol 163,1382,1999) more effectively.
Based on above-mentioned research to mucosal drug delivery system, can bring into play its drug effect in order to make double stranded RNA, can avoid its side effect that brings as much as possible again, people study with the polyinosini nose administration independent.There is people Ceng Danyong polyinosini nose administration to carry out the clinical trial of herpes simplex treatment abroad, but through randomized controlled test strictly, proof single with the polyinosini nose administration fail to respond to any medical treatment (AntimicrobialAgents and Chemotherapy, Sept.1975, P289-294).Domestic somebody is used for flu-prevention with the injection collunarium of polyinosini.But result of study shows that single effect with the polyinosini nose administration is desirable not to the utmost.
Polycationic compounds has chitosan (chitosan, chitosan; 1,4-alpha-amido-α-deoxidation-callose), derivant, polylysine and poly arginine etc. such as part acyl groupization, alkylated chitosan.Chitosan is a kind of natural cation polysaccharide; derive from for example chitin in shrimp Eriocheir sinensis, insecticide and other the no Vertebrate shells of Crustacean; it is a kind of natural macromolecule amylose body that obtains through acetylation; also being present in the zymic cell wall of fungus, is the only polysaccharide that contains the free amine group basic group of occurring in nature.It comprises glucosamine copolymer and nitrogen-acetylglucosamine, wherein contains hydrophilic hydroxyl and protonated amino under certain condition, and amino pKa is 6.5.It has avirulence, help the effect of oozing, bioadhesive, the favorable tissue compatibility, biological degradability, easily be prepared to the characteristics of microparticle and nano-particle, can be as promoting saturating mucosa to absorb.For example, United States Patent (USP) 6391318; AdvancedDrug Delivery Reviews 51,81,2001 has reported the carrier via intranasal application administration immune animal of chitosan as polypeptide and dna vaccination.At present chitosan has been taken in European Pharmacopoeia as pharmaceutic adjuvant, U.S. FDA also approved it be used for medicine and food.Polylysine and poly arginine are artificial synthetic polycationic compounds.
The mucosal drug delivery of polyinosini and mismatch analog thereof, derivant, is processed and is presented at the picked-up by mucosa dependency lymphoreticular tissue, inducement interferon in mucosa and blood simultaneously, and avoid injecting the side effect such as heating that brought effectively.Therefore, be necessary how promoting polyinosini and derivant thereof to study in the absorption and the absorption of mucous membrane tissue.
Summary of the invention
An object of the present invention is to provide a kind of mucosa absorption ingestion type medicinal composition for drawing out interferon, polycationic compounds in this Pharmaceutical composition can promote absorption and the picked-up at mucous membrane tissue of the derivant of polyinosini, polyinosini and their pharmaceutical salts effectively, combined effect is in mucosa associated lymphoid tissue, activating immune system.
Mucosa absorption ingestion type medicinal composition for drawing out interferon of the present invention, contain a, b two class materials in this Pharmaceutical composition:
A, one or more, be selected from polyinosini (polyinosinic acid-polycytidylicacid; Polyinosinic Acid-Polycytidylic Acid; Poly I:C), the material in the derivant of polyinosini and their pharmaceutically acceptable salts;
B, polycationic compounds and/or its pharmaceutically acceptable salt;
Wherein, the molecular weight of a class material is 3,000-400, and 000 dalton, the molecular weight of b class material is 2,000-600,000 dalton; And the part by weight of a, b two class materials is 1: 10-10: 1, and preferred ratio is 1: 2-1: 3.
Polyinosini derivant of the present invention comprises its mismatch analog, for example polyinosini urine (polyI:C
12U; Commodity are called Ampligen), comprise that also other derivant is for example gathered deoxidation flesh born of the same parents etc.Polyinosini urine forms by mixing unpaired uracil through the polyinosini after modifying along poly ribose cytidylic acid (PolyC) chain.Polyinosini and polyinosini urine is inducement interferon effectively, but the drug effect of polyinosini urine is better, and side effect is also littler.Though poly-deoxidation flesh born of the same parents and some other double stranded RNA, as poly-gland urine (polyadenylic acid and polyuridylic acid), also has certain interferon inducted effect, but only adopt polyinosini and/or polyinosini urine can reach good inducement interferon effect, therefore, a class material can be only to adopt polyinosini and/or polyinosini urine.The pharmaceutical salts of polyinosini or derivatives thereof of the present invention can be its alkali metal salt or its alkali salt, is preferably the sodium salt of polyinosini or derivatives thereof.
Polycationic compounds of the present invention can be chitosan (chitosan; Chitosan; 1,4-alpha-amido-α-deoxidation-callose) and material or its combination such as derivant, polylysine, poly arginine.By metabolism, chitosan, polylysine and poly arginine can both be decomposed fully.But because arginine is a vaso-active substance, so the present invention does not preferably adopt poly arginine.B class material of the present invention is preferably the derivant of chitosan, chitosan, the pharmaceutical salts of chitosan or derivatives thereof, one or more materials in the polylysine.Wherein, the deacetylation of chitosan can be 10-100%, and preferably adopting deacetylation is the chitosan of 60-100%; Its salt can be its non-metal salt, for example its hydrochlorate, its quaternary ammonium salt etc.; Its derivant can be an alkylated chitosan, for example, and methyl chitosan, ethyl chitosan, N-acetyl chitosan, N-methyl chitosan, N-dodecyl chitosan etc.Again and, because b class material only adopts chitosan can reach good effect, therefore b class material of the present invention can be only to adopt chitosan.
The present invention limits the molecular weight of above-mentioned a, b class material, has adopted molecular weight roughly 3, and 000-400,000 daltonian a class material and molecular weight be roughly 2,000-600,000 dalton b class material.A of the present invention, b two class materials all can adopt existing on the market medicinal product.That polyinosini can adopt is existing, molecular weight is 100,000-300,000 daltonian medicinal product.Yet, though molecular weight big as 100,000-400,000 daltonian polyinosini is inducement interferon more, but in theory, 10,000-100,000 daltonian polyinosini molecular weight is less, is absorbed by mucous membrane tissue easilier, therefore, more preferably adopt the interior polyinosini of this molecular weight ranges.Then the inducement interferon effect is relatively poor less than 10,000 daltonian polyinosini.Polyinosini urine can adopt molecular weight 3,000-300,000 daltonian medicinal product.The molecular weight of b class material is preferably 2,000-100,000 dalton.
The present invention is the reason that a class material and b class material make up, b class material is positively charged, a class material is electronegative, and the positive charge of b class material band is more than the negative charge of a class material band, two class materials can be cross-linked with each other and form positively charged polymer (microgranule), this polymer can stick effect with electronegative mucous membrane tissue again, thereby prolonged the time that a class material contacts with mucous membrane tissue, promote a class material permeance mucous membrane tissue, and the picked-up by mucosa dependency lymphoreticular tissue, make it enter following lymphoid tissue.In addition, chitosan and polylysine itself also has certain interferon inducted effect, thereby strengthens effect (the J VetMed Sci.2002 Jul of said composition inducement interferon; 64 (7): 645-8. and Biosci BiotechnolBiochem.1995 Oct; 59 (10): 1842-5.).
By zoopery, proved that the effect of mucosa absorption ingestion type medicinal composition for drawing out interferon of the present invention inducement interferon in mucous membrane tissue and serum obviously is better than singly using polyinosini.
Another object of the present invention provides a kind of mucosa and absorbs the interferon inducted preparation of picked-up type, and said preparation is better than the intravenous injection type preparation of polyinosini in the effect of mucosa position inducement interferon, and its side effect is less.
Mucosa of the present invention absorbs the interferon inducted preparation of picked-up type, adopts Pharmaceutical composition of the present invention, and dosage form can be solution, spray, aerosol or powder spray.Preparation of the present invention can act on mucous membrane tissues such as intestinal mucosa, oropharynx mucosa, nasal mucosa.Preferably, Pharmaceutical composition of the present invention is made nasal drop, spray, aerosol or the powder spray of nasal mucosa, act on the mucous membrane tissue of oral cavity, throat, trachea by the mode of spray nose, collunarium or suction.Can contain in the preparation of the present invention pharmaceutically the acceptable adjuvant and/or can with the medicine of Pharmaceutical composition compatibility of the present invention.For example, can contain interferon, antiviral or antineoplastic dna vaccination, CaCl in the said preparation
2, kanamycin etc., can also contain adjuvants such as suspending agent, solubilizing agent and antiseptic.
Mucosa of the present invention absorbs the interferon inducted preparation of picked-up type by mucosa-immune system and systemic immunity system inducement interferon, plays prevention and effects such as treatment viral infection, antitumor.Because preparation of the present invention has adopted chitosan etc. to have the polycationic compounds of short mucosa Absorption, thereby improves polyinosini, its derivant and their the pharmaceutical salts absorption picked-up degree at mucous membrane tissue widely.And what mucosa absorption ingestion type medicinal composition for drawing out interferon of the present invention adopted is the route of administration that mucosa absorbs picked-up, can not produce the side effect of heating as the interferon inducted medicine of intravenous injection type.
Prepare Pharmaceutical composition of the present invention, the pH of aqueous solution should be transferred to and be lower than the polycationic compounds isoelectric point, IP, the ratio that adds positive charge and negative charge then successively is greater than 1 b class material and a class material.Preferably, the pH of aqueous solution transferred to be lower than 6.5, the ratio that adds positive charge and negative charge then successively is greater than 1 chitosan and polyinosini; More preferably, the pH of aqueous solution is transferred to 5.5-6, the ratio that adds positive charge and load then successively is 2-3: 1 chitosan and polyinosini.
Below in conjunction with embodiment, further specify the present invention, but the present invention is not limited to these embodiment, any on essence spirit of the present invention improvement or substitute, still belong to desired protection domain in claims of the present invention.
The specific embodiment
Main material of the present invention and source thereof:
Strand polyinosinic acid and strand poly Guangdong are opened and are changed pharmaceutical factory all one's life
Chitosan Yufeng Biological Engineering Co. Ltd., Hubei
Polylysine gene company limited
Wistar rat Ji'nan University laboratory animal provides
The brilliant U.S. biological engineering company limited in rat gamma interferon ELISA test kit Shenzhen
Embodiment 1
The prescription of mucosa absorption ingestion type medicinal composition for drawing out interferon of the present invention:
1 3mol chitosan, 6000 dalton fill a prescription
1mol polyinosini 200,000 dalton
2 2mol chitosans, 10,000 dalton fill a prescription
1mol polyinosini 300,000 dalton
1000 unit kanamycin
3 1mol chitosans, 100,000 dalton fill a prescription
1mol polyinosini 50,000 dalton
1000 unit kanamycin
4 10mol chitosans, 500,000 dalton fill a prescription
1mol polyinosini 400,000 dalton
5 1mol chitosans, 600,000 dalton fill a prescription
10mol polyinosini 20,000 dalton
Fill a prescription 62 the gram polylysines 500,000
3 gram polyinosini, 100,000 dalton
71 gram poly arginines, 10,000 dalton fill a prescription
3 gram polyinosini, 100,000 dalton
8 1mol chitosans, 2000 dalton fill a prescription
1mol polyinosini 100,000 dalton
1,000,000 unit kanamycin
0.4mmol CaCl
2
9 1mol chitosans, 200,000 dalton fill a prescription
The 1mol polyinosini is urinated 3000 dalton
10 1mol polylysines, 3000 dalton fill a prescription
2mol polyinosini 100,000 dalton
11 1mol polylysines, 6000 dalton fill a prescription
2mol polyinosini 100,000 dalton
12 3mol polylysines, 10000 dalton fill a prescription
1mol polyinosini sodium salt 100,000 dalton
13 3mol N-acetyl chitosans (30% acetylation), 10,000 dalton fill a prescription
1mol polyinosini 100,000 dalton
The 14 3mol N-methyl chitosan of filling a prescription, 10,000 dalton
1mol polyinosini 100,000 dalton
15 5mol N-dodecyl chitosans, 10,000 dalton fill a prescription
1mol polyinosini 100,000 dalton
The 16 2mol deacetylations of filling a prescription reach 95% chitosan 10,000 dalton
1mol polyinosini 100,000 dalton
17 2mol chitosan hydrochlorate, 600,000 dalton fill a prescription
1mol polyinosini sodium salt 100,000 dalton
Preparation method:
(1) under agitation, 0.6 gram-molecular weight is about 3, and 000-6,000 daltonian chitosan are dissolved in 200 milliliters of 1%HCl solution, with 1N NaOH the pH of mixed liquor are transferred to 5.5.
(2) polyinosini prepares by existing polymerization: respectively 0.2 gram strand polyinosinic acid is dissolved in 0.15MNaCl-pH7.2,0.006M phosphate, 0.212 gram strand poly is dissolved in 0.15MNaCl-pH7.2,0.006M phosphate, then these two kinds of solution are mixed, 45 ℃ of insulations 30 minutes, slowly stir, reduce to then room temperature.With its vacuum drying, make the about 10-30 ten thousand dalton's polyinosini of molecular weight at last, under agitation it is dissolved in 100 milliliters the 0.9%NaCl solution.
(3) mixed liquor that while stirring step (1) is made slowly splashes in the mixed liquor that step (2) makes, pH value of solution is transferred to 6, continue to stir the microgranule that in mixed liquor, generates about 10 minutes, make its homodisperse by stirring, make Pharmaceutical composition of the present invention.
If directly adopt polyinosini, then can save the operation of step (2).Prescription 1-17 all can adopt method for preparing.
Embodiment 2 sprays, solution-type nasal drop
The spray and the solution-type nasal drop of polysaccharide-polyinosini of the present invention, chitosan-polyinosini urine adopt following prescription:
Prescription 1
Polyinosini molecular weight 100,000 dalton 1mg
Chitosan molecule amount 10,000 dalton 10mg
An amount of adjust pH of hydrochloric acid is 5.5
Purified Water 100ml
Prescription 2
Polyinosini molecular weight 300,000 dalton 1mg
Chitosan molecule amount 20,000 dalton 10mg
An amount of adjust pH of hydrochloric acid is 6
Purified Water 100ml
Prescription 3
Polyinosini urine molecular weight 10,000 dalton 10mg
Chitosan molecule amount 10,000 dalton 1mg
An amount of adjust pH of hydrochloric acid is 5.5
Purified Water 100ml
Prescription 4
Polyinosini urine molecular weight 30,000 dalton 10mg
Chitosan molecule amount 20,000 dalton 1mg
An amount of adjust pH of hydrochloric acid is 6
Purified Water 100ml
Prescription 5
Polyinosini molecular weight 100,000 dalton 1mg
Chitosan molecule amount 10,000 dalton 10mg
An amount of adjust pH of hydrochloric acid is 5.5
0.9％NaCl 100ml
The Pharmaceutical composition method routinely that embodiment 1 is made embodiment 1 step 3 adds other auxiliary element, the mixture that makes pack into spray or nasal drop container make mucosa of the present invention and absorb interferon inducted spray of picked-up type or solution-type nasal drop.
Embodiment 3 powder sprays
Chitosan of the present invention-polyinosini powder spray prescription is as follows:
Prescription 1
Polyinosini molecular weight 10-30 ten thousand dalton 1mg
Chitosan molecule amount 10,000 dalton 5mg
Microcrystalline Cellulose 10mg
Prescription 2
Polyinosini molecular weight 200,000 dalton 1mg
Chitosan molecule amount 20,000 dalton 5mg
Microcrystalline Cellulose 10mg
Prescription 3
Polyinosini molecular weight 300,000 dalton 1mg
Chitosan molecule amount 20,000 dalton 5mg
Microcrystalline Cellulose 10mg
Preparation method
The Pharmaceutical composition that embodiment 1 step 3 is made carries out vacuum drying to constant weight for 100 milliliters, is crushed into fine powder, makes the interferon inducted powder spray of mucosa absorption-type.
4 solutions of embodiment
The prescription of polylysine of the present invention-polyinosini microgranule solution is as follows:
Prescription 1
Polylysine molecular weight 4000 dalton 3mol
Strand polyinosinic acid 1mol
Strand poly 1mol
Prescription 2
Polylysine molecular weight 8000 dalton 3mol
Strand polyinosinic acid 1mol
Strand poly 1mol
Prescription 3
Polylysine molecular weight 15000 dalton 3mol
Strand polyinosinic acid 1mol
Strand poly 1mol
Preparation method:
(1) polylysine under agitation is dissolved in 0.6 gram, the daltonian polylysine of the about 3000-6000 of molecular weight in 200 milliliters, 1%HCl solution, with 1NNaOH pH is transferred to 7.4.
(2) the existing polymerization preparation of polyinosini: strand polyinosinic acid and strand poly, weighing 0.2 gram strand polyinosinic acid and 0.212 restrains the strand poly, is dissolved in the phosphate of the NaCl-pH7.20.006M of 0.15M respectively, and with two kinds of liquid mixing.After the mixing,, behind slowly stirring, cooling, the vacuum drying, get the about 10-30 ten thousand dalton's polyinosini of molecular weight 45 ℃ of insulations 30 minutes.Again under agitation, the polyinosini with above-mentioned 0.15 gram is dissolved in 100 milliliters the 0.9%NaCl solution.
(3) while stirring (1) liquid is slowly splashed into (2) liquid, and then stir about 10 minutes, the microgranule that generates in mixed liquor makes its homodisperse by stirring.
Embodiment 5 powder
With 100 milliliters of the solution of the polylysine of embodiment 4 preparation and polyinosini, carry out vacuum drying to constant weight, pulverize then, dry powder.
The experiment of embodiment 6 effects
The experiment of inducing rat mucosa-immune system and systemic immunity system to produce interferon with the solution-type nasal drop of chitosan-polyinosini of the present invention of embodiment 2.
One, experiment purpose: the solution-type nasal drop of embodiment 2 is induced the rat IFN effect compare, draw solution-type nasal drop of the present invention and whether be better than single conclusion of using the polyinosini injection with single effect with the polyinosini injection.
Two, experimental procedure
1, laboratory animal and grouping: 2-3 monthly age male Wistar rat.10 of rats are cooked own control, promptly 10 whiles as collunarium before matched group, select 5 to do polyinosini injection collunarium group (1mg polyinosini/milliliter) then at random, do chitosan-polyinosini collunarium group (chitosan-polyinosini makes according to the method for embodiment 2, and its concentration is adjusted into 1mg polyinosini/milliliter) for other 5.The processing of each group is as follows:
1) matched group before the collunarium: collect every rat collunarium preceding nasopharynx part flushing liquor and serum;
2) injection collunarium group and chitosan-polyinosini collunarium group: rat is accepted 6 injection collunariums or chitosan-polyinosini collunarium respectively altogether in two days, and each about 3-6 hour at interval, then, collection nasopharynx part flushing liquor and serum after 12 hours.At interval three weeks were cleaned after dates, and 5 of former received injection collunarium change with 5 that accept chitosan-polyinosini collunarium, by testing with quadrat method.
2, the collection of rat nose flushing liquor
Behind the etherization rat, 0.5mlPBS upwards washes nose from the trachea end, washes 3 times, and 1.5ml collects from the effusive flushing liquor of nasopharynx altogether, and flushing liquor centrifugal (3000r/min) 10 minutes is collected supernatant, and-20 ℃ of preservations are to be measured.
3, serum is collected
Behind the etherization rat, from 3 milliliters of rat tail vein blood drawings, be collected in vitro, 37 ℃ of incubators were placed 30 minutes, and 4 ℃ of refrigerators were placed 1 hour, separation of serum ,-20 ℃ of preservations are to be measured.
4, the mensuration of rat nasopharynx part flushing liquor and serum gamma interferon
Use rat gamma interferon (IFN-γ) ELISA test kit to detect, operation is undertaken by the test kit operating instruction, detects the A value of flushing liquor and serum in microplate reader (450nm).The standard curve of making by standard substance is converted into the corresponding concentration of gamma interferon.The A value that records flushing liquor and serum is as shown in table 1:
The compositions of table 1 chitosan and polyinosini induces the influence of gamma interferon to rat
| Group | Flushing liquor | Serum |
| Group polyinosini injection collunarium group chitosan+polyinosini collunarium group before the collunarium | 14.6±3.4 22.1±4.6 31.5±3.9 | 26.8±5.3 39.3±13.74 63.2±19.2 |
Three, the criterion of experimental result: through the t check, the solution-type nasal drop collunarium group of embodiment 2 is compared with polyinosini injection collunarium group with single, and significant difference is arranged.
Four, conclusion: chitosan and polyinosini solution-type nasal drop can significantly increase polyinosini and induce rat mucosa-immune system and systemic immunity system to produce the effect of interferon through nasal mucosa.
Embodiment 7
Powder spray with embodiment 3 is observed the effect of treatment people's oral cavity herpes simplex.Concrete experimental technique is as follows: select 20 routine oral cavity herpes simplex patients at random, be divided into medication group and blank group, every group 10 people.The medication group uses the powder of embodiment 3 to spray nose 3-5 time every day.The blank group is not carried out administration.
Observed result: treatment group cure time is 3 ± 1.6 days, and blank group cure time is 5 ± 1.3 days.
Conclusion: though the blank group can be fully recovered voluntarily, the required time is longer.The medication group on average shifts to an earlier date 1-2 days than blank group cure time, and two groups result has significant difference.Prove that mucosa of the present invention absorbs the effect that the interferon inducted powder spray of picked-up type has good curing people's oral cavity herpes simplex.
Claims (10)
1, a kind of mucosa absorption ingestion type medicinal composition for drawing out interferon, it contains a, b two class materials:
A, one or more, the derivant that is selected from polyinosini, polyinosini and the material in the pharmaceutically acceptable salt thereof;
B, polycationic compounds and/or its pharmaceutically acceptable salt;
Wherein, described a class molecular weight of material is 3,000-400, and 000 dalton, described b class molecular weight of material is 2,000-600,000 dalton, and the part by weight of described a, b two class materials is 1: 10-10: 1.
2, Pharmaceutical composition as claimed in claim 1 is characterized in that, described polycationic compounds is one or more the material as next group of being selected from: the derivant of chitosan, chitosan, polylysine and poly arginine.
3, Pharmaceutical composition as claimed in claim 2 is characterized in that, the derivant of described chitosan is acetylated chitosan sugar or alkylated chitosan.
4, Pharmaceutical composition as claimed in claim 1 is characterized in that, described a class material is polyinosini and/or polyinosini urine, and described b class material is chitosan and/or its pharmaceutical salts.
5, Pharmaceutical composition as claimed in claim 4 is characterized in that, described a class material is a polyinosini.
As the described Pharmaceutical composition of one of claim 1-5, it is characterized in that 6, the molecular weight of described polyinosini is 10,000-400,000 dalton is preferably 10,000-100,000 dalton.
7, Pharmaceutical composition as claimed in claim 4 is characterized in that, the molecular weight of described polyinosini urine is 3,000-100,000 dalton.
As the described Pharmaceutical composition of one of claim 2-5, it is characterized in that 8, the molecular weight of described chitosan is 2,000-10,000 dalton.
As claim 1,4 or 5 described Pharmaceutical compositions, it is characterized in that 9, the ratio of described a, b two class materials is 1: 2-1: 3.
10, a kind of mucosa absorbs the interferon inducted preparation of picked-up type, it is characterized in that described preparation has adopted the described Pharmaceutical composition of one of claim 1-9, and described preparation is solution, spray, aerosol or powder spray.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104706580A (en) * | 2015-03-25 | 2015-06-17 | 肇庆大华农生物药品有限公司 | Veterinary interferon inducer and preparation method thereof |
| CN105396130A (en) * | 2015-11-10 | 2016-03-16 | 林海祥 | Polyriboinosinic polyribo-cytoidylic acid (PIC), ammonia and calcium adjuvant and vaccine containing same |
| CN110898014A (en) * | 2019-12-09 | 2020-03-24 | 美亚药业海安有限公司 | Preparation method of polyuridylic acid |
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2005
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104706580A (en) * | 2015-03-25 | 2015-06-17 | 肇庆大华农生物药品有限公司 | Veterinary interferon inducer and preparation method thereof |
| CN104706580B (en) * | 2015-03-25 | 2017-11-10 | 华南农业大学 | A kind of interferon inducer for animals and preparation method thereof |
| CN105396130A (en) * | 2015-11-10 | 2016-03-16 | 林海祥 | Polyriboinosinic polyribo-cytoidylic acid (PIC), ammonia and calcium adjuvant and vaccine containing same |
| CN110898014A (en) * | 2019-12-09 | 2020-03-24 | 美亚药业海安有限公司 | Preparation method of polyuridylic acid |
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