CN1660441A - Transmission system of drug for nasal cavity of containing trehalose and byaluronic acid, and preparation method - Google Patents
Transmission system of drug for nasal cavity of containing trehalose and byaluronic acid, and preparation method Download PDFInfo
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- CN1660441A CN1660441A CN2004100755489A CN200410075548A CN1660441A CN 1660441 A CN1660441 A CN 1660441A CN 2004100755489 A CN2004100755489 A CN 2004100755489A CN 200410075548 A CN200410075548 A CN 200410075548A CN 1660441 A CN1660441 A CN 1660441A
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- nasal cavity
- transmission system
- trehalose
- glass acid
- applied medicine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
Abstract
A nasal medicine delivery system for preventing and treating various rhinitises, epistaxis, nasosinusitis, etc contains trehalose, hyaluronic acid and medicinal additive.
Description
Technical field:
Delivery system) and preparation method thereof the invention belongs to field of pharmaceutical technology, is a kind of trehalose (English: trehalose) and the nasal cavity applied medicine transmission system of glass acid (English: hyaluronic acid also claims hyaluronic acid) (English: that contains.
Background technology:
There is significant disadvantages in traditional nasal cavity local application preparation, and for example, behind traditional nasal drop collunarium, the very fast loss of medicine even make that the medicine biological utilisation is low, the of short duration frequent collunarium of effect, also is difficult to reach ideal effect sometimes.In addition, some nasal drop and nasal spray also exist strong or unstability of zest or whole body to absorb shortcomings such as toxicity is big.These have all restricted the application and the development of conventional nasal medication.For addressing these problems, people wish research and use the nasal cavity applied medicine transmission system (English: delivery system), to improve above-mentioned deficiency.
According to the deficiency of traditional nasal cavity local application, people imagine ideal nasal cavity applied medicine transmission system should possess following characteristics simultaneously: but the action time of prolong drug; Can strengthen the absorption of medicine; Can improve bioavailability of medicament; Can reduce the toxicity of medicine, particularly general toxicity; But the stability of prolong drug and shelf-life; Can improve the adaptability of nasal cavity to environment; Has excellent biological compatibility etc.The present main component stickiness excipient of a class nasal cavity applied medicine transmission system of listing, for example: cellulose family, polyvinyl alcohol etc., only have the effect of adhesion-promoting, only prolonged the action time of medicine to a certain extent at nose.This compares with ideal nasal cavity applied medicine transmission system, differs greatly.
Trehalose extensively is present in whole biosphere, comprises antibacterial, fungus, insecticide, other plant and animal, and it has special protective effect to biomolecule.
Resist drying characteristic (" water substitutes " effect): trehalose is a kind of disaccharidase that plays crucial protective effect in dehydration; it can make many biologies under abnormal condition; still original activity can be kept as high temperature, dehydration, when freezing, dry, the resist drying of cell self, anti-refrigerating capacity can be fundamentally improved.
The effect of stabilate film: people's nasal membrane also is a biomembrane, and trehalose can make the film fat under dehydration conditions still be in mesomorphic state by reducing phase transition temperature, thereby plays the biomembranous effect of protection.
Protective effect to biomolecule such as protein: trehalose has significant protective effect to the living matter of dehydrate, even in exsiccant environment extremely, it is biomolecule such as stable protein well, and it is not damaged.
The effect of preparation stabilization agent and antistaling agent: trehalose is widely used as preparation stabilization agent and antistaling agent, this be other glucide can not compare.
As seen from the above, trehalose can enter in the cell, directly acts on cell, brings into play its unique water and substitutes the stress factor effect, improves resist drying, the anti-refrigerating capacity of cell, thereby improves the ability of cell adapted environment; Can keep the stable of biomolecule such as biomembrane, protein and nasal cavity tissue, alleviate toxicity and the general toxicity of medicine the nasal cavity normal structure; Can be used as the stabilizing agent and the antistaling agent of preparation, in order to strengthen the shelf-life of stability of drug and prolongation preparation; Has excellent biological compatibility etc.
The natural human body that is present in of glass acid, glass acid is many to be that (English: form sodium hyaluronate) exists and uses hyaluronic acid sodium with its sodium salt.Glass acid involved in the present invention comprises the salt of glass acid, i.e. the salt of hyaluronic acid sodium or other glass acid.The glass acidic group originally is a chemically inert material, and it has the unique viscoelasticity and the characteristic of non-Newtonian fluid, and has important pharmacological action and physiological function.
The intelligence moisture-keeping function: glass acid is called as ideal nature moisturizing factor, and the carboxyl in its molecule and other polar group can form hydrogen bond and combine a large amount of water with water.And glass acid also can be regulated water absorption automatically according to the humidity of environment.This intelligent moisture-keeping function can make nasal cavity remain optimum humidity.
Lubrication: the glass acid solution has good viscoelasticity, is that solution is stickiness under the low-rate-of-shear at low collision frequency, can reduce the friction between tissue, is that solution is elasticity under the high shearing at high collision frequency, can avoid tissue injury.
Repair, promote the healing effect: glass acid is that wound does not have indispensable material in the cicatrix reparation, but the nasal membrane damage is repaired in its inflammation-inhibiting reaction.
The adhesion-promoting effect: the viscosity of bioavailability of medicament and medicinal liquid is proportionate within the specific limits, and keeping suitable viscosity is the important prerequisite of the efficient effect of medicine performance.Glass acid can improve the viscosity of medicinal liquid as natural biomacromolecule mucopolysaccharide.
Bioadhesive: glass acid is compared with other high molecular polymer, and identical solution viscosity even lower viscosity but can make medicine obtain higher bioavailability, thereby delay the elimination of medicine, and this mainly depends on the bioadhesive of glass acid.
Slow releasing function: glass acid has the effect that makes medicament slow release, is determined by its molecular specificity.Medicine can be embedded in the macromolecular network structure of glass acid by the non-covalent bond mode, and the glass acid molecule is just as a dynamic molecular sieve, is attached to na-sal cavity surfaces together with the medicine long period.
Non-Newton fluid characteristic: though materials such as synthesising macromolecule copolymer can increase the viscosity of medicinal liquid, thereby prolong medicinal liquid and improve curative effect in the holdup time of nasal membrane, yet used synthesising macromolecule copolymer solution is essentially Newtonian fluid, when viscosity increases to a certain degree, can make the inner sensation that produces sticky discomfort of nasal cavity.And the glass acid solution is a non-Newtonian fluid, has unique viscoelasticity, and viscosity can reduce rapidly under high shearing, has overcome the deficiency that tackifiers such as synthesising macromolecule copolymer exist.
As seen from the above: glass acid can act on intercellular substance and connective tissue, and effect such as improve moisturizing, preserve moisture, lubricate improves the living environment of cell; Can pass through the characteristic and the excellent biological compatibility of its adhesion-promoting, bio-adhesive and slow releasing function and non-Newtonian fluid, prolong drug improves bioavailability of medicament in the retention time of na-sal cavity surfaces, reduces the toxic and side effects of medicine, reduces the zest of medicinal liquid etc.
Summary of the invention:
The objective of the invention is: a kind of novel nasal cavity applied medicine transmission system is provided, and this nasal cavity applied medicine transmission system contains trehalose and glass acid.
The main component of nasal cavity applied medicine transmission system of the present invention is trehalose and glass acid, and its basic comprising is trehalose, glass acid and conventional pharmaceutical formulation adjuvant.
The prescription and the scope of medication of nasal cavity applied medicine transmission system of the present invention are: in 100 milliliters or 100 gram nasal cavity applied medicine transmission systems, wherein trehalose 0.01 ~ 50 restrains, glass acid 0.01 ~ 20 gram, other pharmacological component 0～an amount of, conventional pharmaceutical formulation right amount of auxiliary materials.
Nasal cavity applied medicine transmission system of the present invention can be directly used in the control of rhinitis sicca, also can add pharmacological component, be used for the transmission of pharmacological component, be used for the control of various nasal diseases such as rhinitis sicca, atrophic rhinitis, allergic rhinitis, hypertrophic rhinitis, epistaxis, sinusitis or systemic disease.Wherein pharmacological component comprises antimicrobial drug, non-steroid antiinflammatory drug, Aeroseb-Dex, anti-allergic drug, vasoconstrictor, local anesthetic, remission medicine, promotes healing or other pharmacological component etc.Antibiotics in the antimicrobial drug such as chloromycetin, gentamycin sulfate, polygynax, lincomycin, rifampicin etc.; Du-6859a in the antimicrobial drug such as norfloxacin, levofloxacin, ofloxacin, ciprofloxacin, enoxacin, lomefloxacin, rufloxacin, fleroxacin, pefloxacin etc.; Sulfonamides in the antimicrobial drug such as sulfadiazine etc.; Antiviral class medicine in the antimicrobial drug such as acyclovir, vidarabine, ribavirin etc.; Non-steroid antiinflammatory drug such as diclofenac sodium, piroxicam, meloxicam etc.; Aeroseb-Dex such as dexamethasone sodium phosphate, dexamethasone acetate, hydrocortisone, betamethasone sodium phosphate etc.; Anti-allergic drug such as sodium cromoglicate, ketotifen etc.; Vasoconstrictor such as norepinephrine, hydrochloric acid plug Lip river azoles quinoline, Farial, ephedrine hydrochloride etc.; Local anesthetic such as procaine etc.; Remission medicine such as zinc sulfate, heparin sodium, oxymetazoline, carteolol hydrochloride etc.; Promote healing medicine such as allantoin, chitosan and derivant, chondroitin sulfate etc.; Other pharmacological component such as amino acids, peptide class, phospholipid, cellulose family, polyvinyl alcohol, polyacrylic acid, dextran, vitamin A, card pool nurse, polyvinylpyrrolidone, cholesterol, dextromethorphan hydrobromide, Chinese medicine etc.
Trehalose of the present invention is meant the trehalose in any source, comprise by plant, animal tissue's extraction separation get, microbial fermentation and must reach the genetic engineering preparation and get, etc.Trehalose of the present invention is meant the trehalose of any existence form, comprises trehalose that does not contain water of crystallization and the trehalose that contains water of crystallization, etc.
Glass acid of the present invention is meant the glass acid in any source, comprise by animal tissue's extraction separation get, microbial fermentation and must reach genetic engineering preparation and get, etc.Glass acid of the present invention comprises that glass acid and salt thereof are as: hyaluronic acid sodium (claim not only hyaluronate sodium), glass acid zinc (but also claiming Curiosin) etc.Glass acid of the present invention is meant the glass acid of any relative molecular mass size.
Nasal cavity applied medicine transmission system of the present invention can be prepared into the dosage form of various suitable nose medications, comprises liquid preparation (liquidpreparation), for example: solution (solution), suspensoid (suspension), Emulsion (emulsion); Gel (gel); Unguentum (slurry); Ointment (ointment); Ointment (cream) etc.The preparation method of nasal cavity applied medicine transmission system of the present invention is: if all the components is all water-soluble in the prescription, by the prescription and the consumption of nasal cavity applied medicine transmission system of the present invention, trehalose and glass acid are inserted in the suitable quantity of water, make its dissolving back standby; The agent right amount of auxiliary materials of getting it filled dissolving, as needs, add other pharmacological component dissolving again, after the lysate cooling, add trehalose and glass acid solution, add purified water then to volume, obtain containing dosage forms such as the solution of trehalose and glass acid or gel, after filtration sterilization or dry heat sterilization or moist heat sterilization or the chemosterilization, coating-dividing sealing promptly gets nasal cavity applied medicine transmission system of the present invention.
The preparation method of nasal cavity applied medicine transmission system of the present invention can also be: if in the prescription water insoluble active ingredient is arranged, prescription and consumption by nasal cavity applied medicine transmission system of the present invention, with trehalose and glass acid and other composition, the method for preparing dispersion liquid preparation or unguentum or ointment etc. is routinely prepared, obtain dispersion liquid preparation (comprising liposome liquid, micelle liquid, microemulsion etc.) or dosage forms such as unguentum or ointment, refilter degerming or dry heat sterilization or moist heat sterilization or chemosterilization, seal after the packing, promptly get nasal cavity applied medicine transmission system of the present invention.
The nasal cavity applied medicine transmission system that contains trehalose and glass acid has following significant advantage: 1. trehalose can enter in the cell, directly act on cell, bring into play its unique water and substitute the stress factor effect, improve resist drying, the anti-refrigerating capacity of cell, thereby improve the ability of cell adapted environment; Can keep the stable of biomolecule such as biomembrane, protein and bronchia mucosal, alleviate toxicity and the general toxicity of medicine the nasal cavity normal structure; Can be used as the stabilizing agent of preparation and the antistaling agent of product, in order to prolong the shelf-life of preparation; It has excellent biological compatibility etc.2. glass acid can act on intercellular substance and connective tissue, and effect such as improve moisturizing, preserve moisture, lubricate improves the living environment of cell; Can pass through the characteristic and the excellent biological compatibility of its adhesion-promoting, bio-adhesive, spreading wetting and slow releasing function and non-Newtonian fluid, prolong drug is in the retention time of nasal cavity, improve bioavailability of medicament, reduce the toxic and side effects of medicine, reduce the zest of medicinal liquid, improve the comfort level of collunarium etc.3. use is united in trehalose and glass acid, and pair cell environment from inside to outside all plays protection and improvement effect, has improved the ability of cell adapted adverse circumstances, has improved the living environment of cell simultaneously, replenishes mutually and mutual synergic purpose thereby play; Be used for the nasal cavity applied medicine transmission system, can significantly improve the ability of adverse circumstances such as nasal cavity tissue antagonism is outside dry, freezing, lubricated and moistening nasal cavity tissue; Be beneficial to the absorption of medicine; Strengthen stability of drug; Prolong the shelf-life of preparation; Prolong drug improves bioavailability of medicament in the retention time of na-sal cavity surfaces, plays long-acting and slow releasing function; And can reduce the toxic and side effects of medicine; Reduce the zest of medicinal liquid; Improve the comfort level of collunarium; 4. trehalose is a chemically inert material, this is chemically inert material for the glass acidic group, both almost can be used for the transmission of various pharmacological components, are used to prevent and treat various nasal diseases or systemic diseases such as rhinitis sicca, atrophic rhinitis, allergic rhinitis, hypertrophic rhinitis, epistaxis, sinusitis.
Description of drawings:
Fig. 1 is the molecular structure of trehalose, and (English: molecule trehalose) is to be formed by the condensation of hemiacetal hydroxyl by two glucose molecules to trehalose.Trehalose has multiple existence form, and modal is two hydrate crystals, and it loses water of crystallization, then becomes anhydrous crystalline.No matter be the trehalose that exists with which kind of form, its physicochemical property is all very stable, is chemically inert material.
Fig. 2 is the molecular structure of glass acid, the straight chain mucopolysaccharide that glass acid is made up of for disaccharidase unit glucuronic acid and N-n acetylglucosamine n.
The specific embodiment:
The embodiment of the invention 1:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.5 grams, hyaluronic acid sodium 0.10 gram, sodium chloride 0.70 gram, Borax 0.05 gram, all the other are purified water.
The embodiment of the invention 2:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.0 grams, hyaluronic acid sodium 0.10 gram, sodium chloride 0.75 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 3:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.5, hyaluronic acid sodium 0.10, chloromycetin 0.25 gram, sodium chloride 0.68 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 4:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.5 grams, hyaluronic acid sodium 0.10 gram, levofloxacin 0.3 gram, sodium chloride 0.60 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 5:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.0 grams, hyaluronic acid sodium 0.10 gram, acyclovir 0.01 gram, sodium chloride 0.75 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 6:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 2.0 grams, hyaluronic acid sodium 0.20 gram, diclofenac sodium 0.1 gram, sodium chloride 0.65 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 7:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.5 grams, hyaluronic acid sodium 0.15 gram, dexamethasone sodium phosphate 0.1 gram, sodium chloride 0.72 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 8:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.0 grams, hyaluronic acid sodium 0.20 gram, sodium cromoglicate 1.2 grams, sodium chloride 0.70 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 9:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.0 grams, hyaluronic acid sodium 0.10 gram, norepinephrine 0.02 gram, sodium chloride 0.75 gram, Borax 0.05 gram, Vitamin E acetate 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 10:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 2.0 grams, hyaluronic acid sodium 0.15 gram, zinc sulfate 0.4 gram, sodium chloride 0.62 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 11:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.5 grams, hyaluronic acid sodium 0.10 gram, tropicamide 0.25 gram, sodium chloride 0.68 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 12:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.0 grams, hyaluronic acid sodium 0.10 gram, chondroitin sulfate 3 grams, sodium chloride 0.72 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
The embodiment of the invention 13:
Nasal cavity applied medicine transmission system of the present invention, in 100 milliliters, trehalose 1.0 grams, hyaluronic acid sodium 0.10 gram, dextromethorphan hydrobromide 1.5 grams, sodium chloride 0.72 gram, Borax 0.05 gram, ethyl hydroxybenzoate 0.03 gram, all the other are purified water.
Data 1 of the present invention:
We are example with embodiment 13, are contrast with 1.5% traditional dextromethorphan hydrobromide nasal drop, have investigated trehalose and the glass acid influence to drug bioavailability.The results are shown in Table 1.
Table 1 embodiment of the invention 13 dextromethorphan hydrobromide nasal drop pharmacokinetic parameters
| Group | ?C max(ng/ml) | ????t 1/2(min) | ????AUC(min·ng/ml) |
| Traditional dextromethorphan hydrobromide nasal drop embodiment of the invention 5 | ? ??7.9±3.2 ? ??12.6±2.8 | ? ??176.1±62.2 ? ??221.7±53.2 | ? ????1002.3±293.1 ? ????1760.6±325.3 |
What as can be seen from Table 1, trehalose of the present invention and hyaluronic acid sodium can significantly improve medicine reaches peak concentration (C
Max), biological half-life (t
1/2) and area under the concentration-time curve (AUC), significantly improve bioavailability of medicament.This mainly is adhesion-promoting, bio-adhesive, spreading wetting and the slow releasing function that depends on the effect and the glass acid of trehalose stabilate film.
Data 2 of the present invention:
Traditional chloromycetin nasal drop has a remarkable shortcoming: chloromycetin easily is degraded to glycol and lost efficacy, preparation effect duration weak point.We have carried out study on the stability (accelerated test and long term test) to the embodiment of the invention 3 and the traditional chloromycetin nasal drop that does not contain trehalose and hyaluronic acid sodium.The results are shown in Table 2 and table 3.
Table 2 embodiment of the invention 3 chloromycetin accelerated test testing results
(40 ℃ ± 2 ℃ of temperature, relative humidity 20% ± 2%)
| Time | Traditional chloromycetin nasal drop | The embodiment of the invention 3 |
| (moon) | Chloromycetin accounts for the percentage ratio of labelled amount | The catabolite glycol accounts for the percentage ratio of chloromycetin | Chloromycetin accounts for the percentage ratio of labelled amount | The catabolite glycol accounts for the percentage ratio of chloromycetin |
| ????0 ????1 ????2 ????3 ????4 ????5 ????6 | ????100.02 ????98.13 ????97.03 ????95.77 ????94.55 ????93.12 ????92.03 | ????0.01 ????1.77 ????2.96 ????4.20 ????5.46 ????6.86 ????7.96 | ????100.01 ????99.93 ????99.86 ????99.48 ????99.00 ????98.76 ????98.65 | ????0.01 ????0.06 ????0.13 ????0.51 ????0.99 ????1.23 ????1.34 |
Table 3 embodiment of the invention 3 chloromycetin long term test testing results
(25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10%)
| Time (moon) | Traditional chloromycetin nasal drop | The embodiment of the invention 3 | ||
| Chloromycetin accounts for the percentage ratio of labelled amount | The catabolite glycol accounts for the percentage ratio of chloromycetin | Chloromycetin accounts for the percentage ratio of labelled amount | The catabolite glycol accounts for the percentage ratio of chloromycetin | |
| ????0 ????1 ????2 ????3 ????4 ????5 ????6 ????7 ????8 | ????100.02 ????99.90 ????98.01 ????97.38 ????96.57 ????96.02 ????95.65 ????94.83 ????94.15 | ????0.01 ????0.13 ????1.98 ????2.62 ????3.43 ????3.96 ????4.34 ????5.16 ????5.75 | ????100.01 ????99.92 ????99.91 ????99.76 ????99.67 ????99.56 ????99.51 ????99.45 ????99.37 | ????0.01 ????0.08 ????0.10 ????0.24 ????0.31 ????0.44 ????0.50 ????0.56 ????0.62 |
| ????9 ????10 ????11 ????12 ????13 ????14 ????15 ????16 ????17 ????18 | ????93.67 ????93.01 ????92.45 ????92.17 ????92.01 ????91.13 ????90.24 ????89.11 ????88.08 ????87.18 | ????6.32 ????7.00 ????7.56 ????7.82 ????8.01 ????8.86 ????9.75 ????10.88 ????11.91 ????12.82 | ????99.28 ????99.16 ????98.69 ????98.38 ????98.06 ????97.56 ????97.11 ????96.68 ????96.47 ????96.19 | ????0.71 ????0.84 ????1.30 ????1.62 ????1.95 ????2.43 ????2.89 ????3.31 ????3.53 ????3.81 |
By table 2 and table 3 as can be seen, the invention process 3 can significantly reduce the degraded of chloromycetin.The effect duration of traditional chloromycetin nasal drop was generally 1 year, and the effect duration that contains the chloromycetin nasal drop of trehalose and hyaluronic acid sodium can be 1 year half even longer.
Data 3 of the present invention:
We are contrast with the nasal drop and the normal saline of common commercially available verification treatment, have investigated the curative effect of 2 pairs of rhinitis siccas of the embodiment of the invention.2 of patients one time, 4 times on the one, medication is carried out therapeutic evaluation after 2 weeks.Cure: the xeromycteria ventilation improves, and euosmia, nasal mucosa recover normal; Take a turn for the better: subjective symptoms is significantly improved; Invalid: subjective symptoms does not have obvious improvement.
The therapeutic evaluation of 2 pairs of rhinitis siccas of table 4 embodiment of the invention
| Group | Patient's number | Cure rate (%) | Improvement rate (%) | Inefficiency (%) |
| The common commercially available nasal drop embodiment of the invention 2 of normal saline | ????50 ????50 ????50 | ????16 ????36 ????62 | ????20 ????40 ????36 | ????64 ????24 ????2 |
As can be seen from Table 4, trehalose and glass acid use in conjunction in the nasal cavity applied medicine transmission system, can significantly be improved the rhinitis sicca symptom, effective percentage (cure rate+improvement rate) is 98%; Significantly be better than common commercially available nasal drop and normal saline.
Claims (19)
1, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid is characterized in that containing trehalose and glass acid in the prescription.
2, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 1 is characterized in that the basic comprising of filling a prescription is trehalose, glass acid and conventional dose adjuvant.
3, a kind of as arbitrary described nasal cavity applied medicine transmission system that contains trehalose and glass acid in the claim 1 to 2, it is characterized in that pharmacological component is antimicrobial drug, non-steroid antiinflammatory drug, Aeroseb-Dex, anti-allergic drug, vasoconstrictor, local anesthetic, remission medicine and promotes the healing medicine.
4, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid described in claim 3 is characterized in that the Tri-Biocin in the antimicrobial drug is chloromycetin, gentamycin sulfate, lincomycin and rifampicin.
5, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that the Du-6859a in the antimicrobial drug is norfloxacin, levofloxacin, ofloxacin, ciprofloxacin, lomefloxacin, rufloxacin, fleroxacin and pefloxacin.
6, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that the sulfonamides in the antimicrobial drug is a sulfadiazine.
7, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that antiviral agents is acyclovir, vidarabine and ribavirin.
8, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that non-steroid antiinflammatory drug is diclofenac sodium, piroxicam and meloxicam.
9, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that adrenocortical hormone is dexamethasone sodium phosphate, dexamethasone acetate, hydrocortisone and betamethasone sodium phosphate.
10, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that anti-allergic drug is a sodium cromoglicate.
11, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that vasoconstrictor is norepinephrine, hydrochloric acid plug Lip river azoles quinoline, ephedrine hydrochloride and Farial.
12, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that local anesthetic is a procaine.
13, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that the remission medicine is zinc sulfate, heparin sodium, oxymetazoline and carteolol hydrochloride.
14, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that promoting that the wound healing medicine is allantoin, chitosan and derivant thereof and chondroitin sulfate.
15, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that other pharmacological component is amino acids, peptide class, phospholipid, cellulose ethers, polyvinyl alcohol, polyacrylic acid, dextran, vitamin A, carbomer, polyvinylpyrrolidone, cholesterol and dextromethorphan hydrobromide.
16, a kind of nasal cavity applied medicine transmission system that contains trehalose and glass acid as claimed in claim 3 is characterized in that pharmacological component is the multiple or different classes of multiple of a kind of or same classification.
17, a kind of as arbitrary described nasal cavity applied medicine transmission system that contains trehalose and glass acid in the claim 1 to 3, it is characterized in that in 100 milliliters or 100 gram nasal cavity applied medicine transmission systems, component is trehalose 0.01 ~ 50 gram, glass acid 0.01 ~ 20 gram, other pharmacological component 0 ~ an amount of, pharmaceutical necessities is an amount of.
18, a kind of as arbitrary described nasal cavity applied medicine transmission system that contains trehalose and glass acid in the claim 1 to 3, it is characterized in that its preparation method is: if all the components is all water-soluble in the prescription, prescription and consumption by nasal cavity applied medicine transmission system of the present invention, trehalose and glass acid are inserted in the suitable quantity of water, make its dissolving back standby; The agent right amount of auxiliary materials of getting it filled dissolving, as needs, add other pharmacological component dissolving again, after the lysate cooling, add trehalose and glass acid solution, add purified water then in right amount to volume, obtain containing the pharmaceutical solutions or the gel of trehalose and glass acid, after filtration sterilization or dry heat sterilization or moist heat sterilization or chemosterilization, coating-dividing sealing promptly gets nasal cavity applied medicine transmission system of the present invention.
19, a kind of as arbitrary described nasal cavity applied medicine transmission system that contains trehalose and glass acid in the claim 1 to 3, it is characterized in that its preparation method is: if in the prescription water insoluble active ingredient is arranged, prescription and consumption by nasal cavity applied medicine transmission system of the present invention, with trehalose and glass acid and other composition, the method for preparing dispersion liquid preparation or unguentum or ointment etc. is routinely prepared, obtain dispersion liquid preparation or unguentum or ointment, refilter degerming or dry heat sterilization or moist heat sterilization or chemosterilization, seal after the packing, promptly get nasal cavity applied medicine transmission system of the present invention.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100755489A CN1285382C (en) | 2004-12-20 | 2004-12-20 | Transmission system of drug for nasal cavity of containing trehalose and byaluronic acid, and preparation method |
| PCT/CN2005/002253 WO2006066500A1 (en) | 2004-12-20 | 2005-12-20 | The preparation process of quinazoline derivatives and application for the manufacture for the treatment of tumor disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100755489A CN1285382C (en) | 2004-12-20 | 2004-12-20 | Transmission system of drug for nasal cavity of containing trehalose and byaluronic acid, and preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1660441A true CN1660441A (en) | 2005-08-31 |
| CN1285382C CN1285382C (en) | 2006-11-22 |
Family
ID=35010175
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100755489A Expired - Fee Related CN1285382C (en) | 2004-12-20 | 2004-12-20 | Transmission system of drug for nasal cavity of containing trehalose and byaluronic acid, and preparation method |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1285382C (en) |
| WO (1) | WO2006066500A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006069540A1 (en) * | 2004-12-29 | 2006-07-06 | Ocean University Of China | Burn-treating drug delivery system containing trehalose and hyaluronic acid and its producing method |
| CN102579478A (en) * | 2012-03-30 | 2012-07-18 | 济南康众医药科技开发有限公司 | Application of sodium hyaluronate to preparation of medicines |
| CN104147603A (en) * | 2014-08-04 | 2014-11-19 | 辽宁亿灵科创生物医药科技有限公司 | Application of novel marine algae extractive composition in preventing virus flu |
| CN105381454A (en) * | 2015-12-17 | 2016-03-09 | 齐鲁工业大学 | Nasal cavity wetting agent containing trehalose |
| CN105412913A (en) * | 2015-12-17 | 2016-03-23 | 齐鲁工业大学 | Nasal cavity wetting agent |
| CN115397433A (en) * | 2020-04-17 | 2022-11-25 | 21世纪国际新技术株式会社 | Medicine and nasal spray containing trehalose or trehalose derivatives |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102011114094A1 (en) * | 2011-09-21 | 2013-03-21 | F. Holzer Gmbh | Stimulating and invigorating nasal spray and nose drops |
| CN112006987B (en) * | 2019-12-13 | 2023-04-28 | 吉林省健敷鼻科技有限公司 | Cold compress gel for treating rhinitis and preparation method thereof |
| WO2022261723A1 (en) * | 2021-06-17 | 2022-12-22 | Pant Harshita | Compositions and uses thereof |
| IT202100021659A1 (en) * | 2021-08-10 | 2023-02-10 | A&R Pharma Srl | Topical composition and its use for the nasal treatment of rhinitis |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1065141C (en) * | 1998-05-20 | 2001-05-02 | 北京金源东和化学有限责任公司 | Medicine preparation administrated through nasal mucosa |
| DE10161110A1 (en) * | 2001-12-12 | 2003-06-26 | Ursapharm Arzneimittel Gmbh | Pharmaceutical composition for ophthalmic and rhinological use |
| JP3885204B2 (en) * | 2002-04-16 | 2007-02-21 | 株式会社Ｃａｃ | External agent for promoting cell activity |
| CN1302812C (en) * | 2004-11-30 | 2007-03-07 | 中国海洋大学 | Transmission system of medicine containing trehalose and hyaluronic acid for eye part and its preparation method |
-
2004
- 2004-12-20 CN CNB2004100755489A patent/CN1285382C/en not_active Expired - Fee Related
-
2005
- 2005-12-20 WO PCT/CN2005/002253 patent/WO2006066500A1/en active Application Filing
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006069540A1 (en) * | 2004-12-29 | 2006-07-06 | Ocean University Of China | Burn-treating drug delivery system containing trehalose and hyaluronic acid and its producing method |
| CN1302813C (en) * | 2004-12-29 | 2007-03-07 | 中国海洋大学 | Transmission system for medicine containing trehalose and hyaluronic acid in use for curing burn and preparing method |
| CN102579478A (en) * | 2012-03-30 | 2012-07-18 | 济南康众医药科技开发有限公司 | Application of sodium hyaluronate to preparation of medicines |
| CN104147603A (en) * | 2014-08-04 | 2014-11-19 | 辽宁亿灵科创生物医药科技有限公司 | Application of novel marine algae extractive composition in preventing virus flu |
| CN105381454A (en) * | 2015-12-17 | 2016-03-09 | 齐鲁工业大学 | Nasal cavity wetting agent containing trehalose |
| CN105412913A (en) * | 2015-12-17 | 2016-03-23 | 齐鲁工业大学 | Nasal cavity wetting agent |
| CN105412913B (en) * | 2015-12-17 | 2019-05-14 | 齐鲁工业大学 | A kind of nasal cavity wetting agent |
| CN105381454B (en) * | 2015-12-17 | 2019-05-14 | 齐鲁工业大学 | A kind of nasal cavity wetting agent containing trehalose |
| CN115397433A (en) * | 2020-04-17 | 2022-11-25 | 21世纪国际新技术株式会社 | Medicine and nasal spray containing trehalose or trehalose derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006066500A1 (en) | 2006-06-29 |
| CN1285382C (en) | 2006-11-22 |
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