CN103211801B - One is rapidly-soluble membrane and preparation method thereof in the oral cavity - Google Patents
One is rapidly-soluble membrane and preparation method thereof in the oral cavity Download PDFInfo
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Abstract
The invention discloses one rapidly-soluble membrane and preparation method thereof in the oral cavity, by weight, this membrane agent is made up of following compositions: active constituents of medicine, and 0.1 ~ 70%; Water soluble film-forming material, 30 ~ 90%; Plasticizer, 2 ~ 20%; Disintegrating agent, 0 ~ 5%; Water, 1 ~ 20%; Described medicament active composition is selected from modification or unmodified cobra-venom, Sumatriptan Succinate, Dihydroergotamitie Tartrate, lomerizine hydrochloride or flunarizine hydrochloride.The present invention is rapid-action, avoids lessen the curative effect oral decomposition by gastrointestinal tract.This preparation technology is simple, economical, practical, and is convenient to realize industrialization batch production.
Description
Technical field
The present invention relates to medical art, be specifically related to one and treat joint autoimmune disease, migraine agent rapidly-soluble thin film formulations and preparation method thereof in the oral cavity.
Background technology
Autoimmune disease is that a class cause of disease is complicated, and recurrent exerbation, very harmful commonly encountered diseases, due to most of etiology unknown, treats more difficult.Wherein rheumatism (rheumatoid) property arthritic rate is high, and recurrent exerbation can cause joint deformity, affects function, disability.Simple physical process has been carried out to naja naja atra venom, the object of attenuation synergistic can be reached, modification cobra venom has good inflammation-inhibiting, pain and immunoreactive effect and the arthritic effect for the treatment of Freund adjuvant, can be used for treating rheumatoid arthritis, the diseases such as systemic lupus erythematosus (sle), and oral administration once can produce curative effect every day, immunosuppressive action intensity quite or be better than Tripterygium wilfordii glycosid, but under therapeutic dose, there is no obvious toxic-side effects and cobra venom to thymus, the immune organs such as spleen do not affect, cobra venom suppresses the generation of proinflammatory cytokine, but do not suppress the cytokine of antiinflammatory.In cobra-venom lyophilized powder, 90% is protein, although there is good pharmacological action, lacks rationally effective dosage form at present.Oral instant medicine film provides an ideal route of administration, because the permeability of oral mucosa is good, snake venom oral administration makes snake venom effective ingredient in buccal absorption, can reduce the decomposition of gastrointestinal proteases to snake venom effective ingredient, improves drug effect and easy to use.
The periodical attack disease of migraine Shi Yileiyou family morbidity tendency, show as paroxysmal inclined side pulsatile headache, companion's Nausea and vomiting and photophobia, fall ill again through one section of after date of having a rest.In peace and quiet, dark surrounds or after sleep, headache relief.Before generation of having a headache or when showing effect, can with psychoneural dysfunction.Be 732.1/(10 ten thousand in the migrainous incidence rate of China) people, American-European countries's sickness rate is 1500 ~ 20,00/,(10 ten thousand) people.The World Health Organization (WHO) proposes, and migraine and quadriplegia, mental disorder and dementia have become the most serious chronic functional obstacle disease all, is to have a strong impact on patient work and one of common chronic disease of living.Therefore, migrainous prevention and treatment receive increasing concern.
The intractable migraine headache of recurrent exerbation, can not be alleviated by general out-patient treatment usually.Patient is except the progressivity headache continued, also have a series of physiology and affective symptom, as nausea,vomiting,diarrhea, dehydration, depression, despair even suicidal tendency etc., control by medicines such as Sumatriptan Succinate, Dihydroergotamitie Tartrate, lomerizine hydrochloride, flunarizine hydrochloride, then implement long-term preventive medicine treatment.Wherein, lomerizine hydrochloride (Lomerizinehydrochloride, Lom) is the novel antimigraine developed jointly by Kanebo and Pharmacia & Upjohn company, within 1999, goes on the market first in Japan.As calcium, sodium channel binary antagonist, compared with similar drugs, lomerizine effect is stronger, stronger to cerebrovascular selection, is that a kind of curative effect is better, and the new drug that side effect is lower.
Said medicine shows good therapeutic effect in treatment pain.But treatment pain class medicine, is the dosage forms such as tablet, capsule mostly at present.For the dosage form of emergency case medicine as parts that comes with some shortcomings such as oral cavity disintegration tablet, Sublingual tablet, dispersible tablets, need with special freeze-drier as adopted lyophilization to produce, most of oral cavity disintegration tablet has the large shortcoming of friability, makes troubles to the packaging of tablet, transport and patient consumes.Compared with above-mentioned dosage form, oral instant membrane preparation technology is simple, without friability, easy to carry and preparation prescription proposed by the invention there is not yet bibliographical information.
Summary of the invention
First object of the present invention is, provide a kind of treat autoimmune disease, chronic pain, migrainous rapid solution in the oral cavity and absorb novel thin film preparation.
Second object of the present invention is, provides a kind of and treats autoimmune disease, chronic pain, migrainous rapid solution in the oral cavity the preparation method of Novel thin membrane absorbed.
To achieve the above object of the invention, the technical solution used in the present invention is: one is rapidly-soluble membrane in the oral cavity, and by weight, this membrane agent is made up of following compositions:
Active constituents of medicine, 0.1 ~ 70%; Water soluble film-forming material, 30 ~ 90%; Plasticizer, 2 ~ 20%; Disintegrating agent, 0 ~ 5%; Water, 1 ~ 20%;
Described medicament active composition is selected from modification or unmodified cobra-venom, Sumatriptan Succinate, Dihydroergotamitie Tartrate, lomerizine hydrochloride or flunarizine hydrochloride.
In technique scheme, described water soluble film-forming material is selected from hydroxypropyl methylcellulose, maltodextrin, polyvinyl alcohol, sodium carboxymethyl cellulose, gelatin, hyaluronic acid, polyvinylpyrrolidone, chitosan, ethyl cellulose, the one in cellulose acetate or mixture.
Described water soluble film-forming material is hydroxypropyl methylcellulose and hyaluronic mixture, hydroxypropyl emthylcellulose and hyaluronic acid weight weight ratio are 20 ~ 80: 1, described hydroxypropyl emthylcellulose be the hydroxypropyl emthylcellulose of viscosity 2 ~ 50 centipoise.
Preferred technical scheme, hydroxypropyl emthylcellulose and hyaluronic acid weight weight ratio are 50 ~ 70: 1, described hydroxypropyl emthylcellulose be the hydroxypropyl emthylcellulose of viscosity 5 ~ 15 centipoise.
Described plasticizer is selected from propylene glycol, PEG400, glycerol, the one in triethyl citrate or mixture; Described disintegrating agent is selected from polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, the one in pregelatinized Starch or mixture.
The preparation method of rapidly-soluble membrane, comprises the following steps: in the oral cavity
1) by soluble in water for the water soluble ingredient except water-soluble polymer, aqueous solution is obtained;
2) join in aqueous solution by biological at least one acceptable water-soluble polymer under stirring, abundant dispersed with stirring obtains polymer gel;
3) in above-mentioned polymer gel, add plasticizer and stir;
4) add active component and other component and stir;
5) degassed, polymer gel is spread evenly across on flat board;
6) blast heating is dry, and heat drying temperature is 40-60 DEG C, and cutting, obtains oral instant membrane.
Because technique scheme is used, the present invention compared with prior art has following advantages:
Physiology provided by the invention can accept thin film, discharges medicine in the oral cavity, rapidly by buccal absorption, concerning the approach emergency patients being a kind of rapid-action administration the best.Be particularly suitable for adhesion and be rapidly dissolved in the oral cavity of user.Fast dissolve films, release of therapeutic agents, and direct oral cavity mucosa absorbs pharmaceutically active substances fast thus plays drug effect, for pain class disease, shortening the Principle of Pain time is significantly, also embodies the feature of this one dosage type low temperature.For biopharmaceutical macromolecular drug, drag residence is absorbed at oral mucosa, avoids lessen the curative effect oral decomposition by gastrointestinal tract.This preparation technology is simple, economical, practical, and is convenient to realize industrialization batch production.
Accompanying drawing explanation
Fig. 1 is the impact that after Chinese cobra venom oral instant membrane administration 3h, Dichlorodiphenyl Acetate induced pain licks the foot time;
Fig. 2 for after Chinese cobra venom oral instant membrane administration 3h on the pain mice caused by hot plate lick foot the time impact;
Fig. 3 is that after Chinese cobra venom administration 3h, PARA FORMALDEHYDE PRILLS(91,95) causes the impact that scorching induced pain licks the foot time;
Fig. 4 is the photo of oral instant membrane sample;
Fig. 5 is the scanning electron microscope (SEM) photograph of oral instant membrane;
Fig. 6 is the X-ray diffracting spectrum of oral instant membrane.
Detailed description of the invention
Below in conjunction with drawings and Examples, the invention will be further described:
Embodiment 1:
Oral instant membrane disintegration time mensuration method:
100mL distilled water is put into 100mL beaker to be placed on magnetic stirrer, 37 DEG C of waters bath with thermostatic control, speed of agitator 50r/min, appoints and to get it filled film 10 (1cm × 1cm), get one at every turn, is clipped in by test membrane water-bath put into by clip to start timing.The time of record membrane fragmentation and the disintegration of membrane.
Embodiment 2:
Oral instant membrane For Measuring Mechanical Properties method:
Adopt universal material experiment instrument (Instron3365), film is cut to about 2cm × 0.5cm size (balancing a week under 43%RH humidity), draw speed 5mmmin
-1, every bar membrane is all longitudinally stretched, until film fracture.The mechanical performance of oral instant membrane, as elastic modelling quantity (EM), extends described in percentage ratio being calculated as follows of (E%).Its Elastic Modulus refers in elastic deformation stage, the ratio of applied stress and adaptability to changes, and formula below can be used to calculate:
Elastic modelling quantity=applied stress/adaptability to changes/cross-sectional area
Calculated by following formula and extend percentage ratio:
Extend percentage ratio=length at break-the original length/the original length × 100
Embodiment 3:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 3g |
| Glycerol | 0.3 mL |
| Active component | In right amount |
| Purified water | 15mL |
Specific operation process: hydroxypropyl emthylcellulose (5 centipoise) is under agitation dispersed in purified water, and abundant dispersing and dissolving obtains gel, adds recipe quantity glycerol, active component is added under stirring, abundant dispersion, degassed, above-mentioned gel is adopted automatic coating machine, be spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is general.Disintegration is 92s.
Embodiment 4:
| Component | Content |
| Polyvinyl alcohol | 1.2g |
| Glycerol | 0.3 mL |
| Active component | In right amount |
| Purified water | 15mL |
Specific operation process: polyvinyl alcohol is under agitation dispersed in purified water, abundant dispersing and dissolving obtains gel, under stirring, add active component, add recipe quantity glycerol, abundant dispersion, degassed, above-mentioned gel is adopted automatic coating machine, be spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is good, and viscosity is large.Disintegration is 42s.
Embodiment 5:
| Component | Content |
| Polyvinyl alcohol | 1.0g |
| Hyaluronic acid | 0.02g |
| Glycerol | 0.3 mL |
| Active component | In right amount |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, polyvinyl alcohol is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity glycerol, under stirring, add active component, fully disperse, degassed, above-mentioned gel is adopted automatic coating machine, is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, and cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is good, and viscosity is large.Disintegration is 31s.
Embodiment 6:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 1.2g |
| Hyaluronic acid | 0.02g |
| Glycerol | 0.3 mL |
| Active component | In right amount |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, hydroxypropyl emthylcellulose (5 centipoise) is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity glycerol, under stirring, add active component, fully disperse, degassed, above-mentioned gel is adopted automatic coating machine, is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, and cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is good.Disintegration is 47s.
Embodiment 7:
| Component | Content |
| Hydroxypropyl emthylcellulose (15 centipoise) | 0.8 g |
| Hyaluronic acid | 0.02g |
| Glycerol | 0.3 mL |
| Active component | In right amount |
| Purified water | 15mL |
Specific operation process: hyaluronic acid to be under agitation scattered in purified water and to dissolve, hydroxypropyl emthylcellulose (15 centipoise) under agitation being added above-mentioned solution, adds recipe quantity glycerol, abundant dispersing and dissolving obtains gel, adds active component, fully disperse under stirring, degassed, above-mentioned gel is adopted automatic coating machine, is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, and cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is good.Disintegration is 47s.
Embodiment 8:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Glycerol | 0.3 mL |
| Active component | In right amount |
| Carboxymethyl starch sodium | 0.02g |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, hydroxypropyl emthylcellulose (5 centipoise) is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity glycerol, under stirring, add active component, carboxymethyl starch sodium, abundant dispersion, degassed, above-mentioned gel is adopted automatic coating machine, be spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is general.Disintegration is 18s.
Embodiment 9:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Glycerol | 0.3 mL |
| Active component | In right amount |
| Low-substituted hydroxypropyl cellulose | 0.02g |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, hydroxypropyl emthylcellulose (5 centipoise) is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity glycerol, under stirring, add active component, low-substituted hydroxypropyl cellulose, abundant dispersion, degassed, above-mentioned gel is adopted automatic coating machine, be spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is good.Disintegration is 27s.
Embodiment 10:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Glycerol | 0.3 mL |
| Active component | In right amount |
| Polyvinylpolypyrrolidone | 0.02g |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, hydroxypropyl emthylcellulose (5 centipoise) is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity glycerol, under stirring, add active component, polyvinylpolypyrrolidone, abundant dispersion, degassed, above-mentioned gel is adopted automatic coating machine, be spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is good.Disintegration is 22s.
Embodiment 11:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Glycerol | 0.3 mL |
| Active component | In right amount |
| Pregelatinized Starch | 0.02g |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, hydroxypropyl emthylcellulose (5 centipoise) is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity glycerol, under stirring, add active component, pregelatinized Starch, abundant dispersion, degassed, above-mentioned gel is adopted automatic coating machine, be spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is good.Disintegration is 22s.
Embodiment 12:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Propylene glycol | 0.3 mL |
| Active component | In right amount |
| Pregelatinized Starch | 0.02g |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, hydroxypropyl emthylcellulose (5 centipoise) is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity propylene glycol, under stirring, add active component, pregelatinized Starch, abundant dispersion, degassed, above-mentioned gel is adopted automatic coating machine, be spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is general.Disintegration is 25s.
Embodiment 13:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Propylene glycol | 0.3 mL |
| PEG400 | 0.3mL |
| Active component | In right amount |
| Pregelatinized Starch | 0.02g |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, hydroxypropyl emthylcellulose (5 centipoise) is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity propylene glycol, PEG400, under stirring, add active component, pregelatinized Starch, fully disperses, degassed, above-mentioned gel is adopted automatic coating machine, is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, and cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is good.Disintegration is 26s.
Embodiment 14:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Propylene glycol | 0.3 mL |
| Triethyl citrate | 0.3mL |
| Active component | In right amount |
| Pregelatinized Starch | 0.02g |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, hydroxypropyl emthylcellulose (5 centipoise) is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity propylene glycol, triethyl citrate, under stirring, add active component, pregelatinized Starch, fully disperses, degassed, above-mentioned gel is adopted automatic coating machine, is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, and cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is general.Disintegration is 30s.
Embodiment 15:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 0.8 g |
| Hyaluronic acid | 0.02g |
| Propylene glycol | 0.3 mL |
| PEG400 | 0.3mL |
| Active component | In right amount |
| Pregelatinized Starch | 0.02g |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, hydroxypropyl emthylcellulose (5 centipoise) is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity propylene glycol, pregelatinized Starch, under stirring, add active component, pregelatinized Starch, fully disperses, degassed, above-mentioned gel is adopted automatic coating machine, is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, and cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is general, easy friability.Disintegration is 18s.
Embodiment 16:
| Component | Content |
| Hydroxypropyl emthylcellulose (5 centipoise) | 1.6 g |
| Hyaluronic acid | 0.04g |
| Propylene glycol | 0.3 mL |
| PEG400 | 0.3mL |
| Active component | In right amount |
| Pregelatinized Starch | 0.02g |
| Purified water | 15mL |
Specific operation process: being under agitation scattered in by hyaluronic acid in purified water and dissolving, hydroxypropyl emthylcellulose (5 centipoise) is under agitation added above-mentioned solution, and abundant dispersing and dissolving obtains gel, add recipe quantity propylene glycol, triethyl citrate, under stirring, add active component, pregelatinized Starch, fully disperses, degassed, above-mentioned gel is adopted automatic coating machine, is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, and cutting, obtains oral instant membrane.This film is transparent, and in light yellow, demoulding performance is good, and pliability is general.Disintegration is 28s.
Embodiment 17:
The pain reaction that 1 Chinese cobra venom oral instant medicine film suppresses acetic acid to cause:
Acetic acid writhing test is the experimental technique of conventional classical screening acute pain analgesic.Because this experimental implementation is simple, it is therefore the common model of evaluating and screening analgesic.ICR mice is divided at random 5 groups (n=10-12) female half and half, body weight 18-22g: saline control group, Chinese cobra venom oral instant membrane small dose group (10 μ g/kg), middle dosage group (30 μ g/kg), heavy dose of group (90 μ g/kg), aspirin (100mg/kg), Chinese cobra venom oral instant membrane oral cavity buccal, saline control group and aspirin gastric infusion, every day 1 time, continuous 5 days, after last administration 3h, with 0.8% acetum lumbar injection, every mice 0.2ml, each Mus writhing number of times in 15min after record injection.The heavy dose of inflammatory pain obviously reduced caused by acetic acid of snake venom, is better than in snake venom, low dosage.The results are shown in Figure 3 for PARA FORMALDEHYDE PRILLS(91,95) after Chinese cobra venom oral instant membrane administration 3h cause scorching induced pain add the foot time impact (
± SD, n=11-12); * P<0.05, * * P<0.01 compared with matched group.
The pain reaction that 2 Chinese cobra venom oral instant medicine films suppress hot plate to cause:
Hot plate method equipment is simple, easy to use, and observation index is clear and definite, and little to tissue loss, latency of pain response is longer, is convenient to observe and measure less difference between medicine, comparative drug analgesic activity power, speed and persistent period.KM mice is divided at random 5 groups (n=10) female half and half, body weight 18-22g: saline control group, Chinese cobra venom oral instant membrane small dose group (10 μ g/kg), middle dosage group (30 μ g/kg), heavy dose of group (90 μ g/kg), morphine (5mg/kg), morphine positive controls is in test lumbar injection 1 time on the same day (0.1ml/10g), Chinese cobra venom oral instant membrane oral cavity buccal, saline control group gastric infusion, every day 1 time, continuous 5 days, after last administration, 30min, 3h, 6h, 9h measured pain threshold respectively.What in snake venom, dosage and heavy dose of snake venom obviously reduced pain mice caused by hot plate adds the sufficient time, is better than snake venom low dosage, and when 6h, has significant difference compared with matched group.The results are shown in Figure 4 for after Chinese cobra venom oral instant membrane administration 3h on the pain mice caused by hot plate add foot the time impact (
± SD, n=10); * P<0.05, * * P<0.01 compared with matched group.
3 Chinese cobra venom oral instant medicine films suppress formaldehyde-caused pain reaction:
Formaldehyde causes the valid model that inflammatory pain model is the constant pain that chemical noxious stimulation causes, and is widely used in the research of Theory of Pain Mechanism and the screening of analgesic.KM mice is divided at random 5 groups (n=11-12), female half and half, body weight 18-22g: saline control group, Chinese cobra venom oral instant membrane small dose group (10 μ g/kg), middle dosage group (30 μ g/kg), heavy dose of group (90 μ g/kg), aspirin (100mg/kg), Chinese cobra venom oral instant membrane oral cavity buccal, saline control group and aspirin gastric infusion, every day 1 time, continuous 5 days, after last administration 3h, in right side of mice vola subcutaneous injection 1.5% formalin 20 μ l induced pain, put back in transparent observing container immediately, record mice respectively with timer and add the sufficient time (second), record two phases.Ith phase is 0 ~ 5min after acute stage and induced pain, and the IIth phase is 15 ~ 30min after tetanic phase and induced pain.What in snake venom, dosage and heavy dose of snake venom obviously reduced inflammatory pain mice caused by formaldehyde adds the sufficient time, is better than snake venom low dosage.The results are shown in Figure 5 for PARA FORMALDEHYDE PRILLS(91,95) after Chinese cobra venom administration 3h cause scorching induced pain add the foot time impact (
± SD, n=11-12); * P<0.05, * * P<0.01, * * * P<0.001 compared with matched group.
Claims (4)
1. a rapidly-soluble membrane in the oral cavity, it is characterized in that, by weight, this membrane agent is made up of following compositions:
Active constituents of medicine, 0.1 ~ 70%; Water soluble film-forming material, 30 ~ 90%; Plasticizer, 2 ~ 20%; Disintegrating agent, 0 ~ 5%; Water, 1 ~ 20%, each constituent content sum equals 100%;
Described medicament active composition is selected from modification or unmodified cobra-venom, Sumatriptan Succinate, Dihydroergotamitie Tartrate, lomerizine hydrochloride or flunarizine hydrochloride;
Described water soluble film-forming material is hydroxypropyl emthylcellulose and hyaluronic mixture, and hydroxypropyl emthylcellulose and hyaluronic acid weight proportion are 20 ~ 80: 1, and the viscosity of described hydroxypropyl emthylcellulose is 2 ~ 50 centipoises;
Described plasticizer is selected from propylene glycol, PEG400, glycerol, the one in triethyl citrate or mixture.
2. rapidly-soluble membrane in the oral cavity according to claim 1, is characterized in that: hydroxypropyl emthylcellulose and hyaluronic acid weight proportion are 50 ~ 70: 1, the viscosity of described hydroxypropyl emthylcellulose is 5 ~ 15 centipoises.
3. rapidly-soluble membrane in the oral cavity according to claim 1, is characterized in that: described disintegrating agent is selected from polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, the one in pregelatinized Starch or mixture.
4. the preparation method of arbitrary rapidly-soluble membrane in the oral cavity in claims 1 to 3, is characterized in that comprising the following steps:
1) hyaluronic acid to be under agitation scattered in purified water and to dissolve, obtaining aqueous solution;
2) then join in aqueous solution by hydroxypropyl emthylcellulose under stirring, abundant dispersed with stirring obtains polymer gel;
3) in above-mentioned polymer gel, add plasticizer and stir;
4) add active component and other components and stir;
5) degassed, polymer gel is spread evenly across on flat board;
6) blast heating is dry, and heat drying temperature is 40-60 DEG C, and cutting, obtains oral instant membrane.
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| US10952959B2 (en) | 2017-01-11 | 2021-03-23 | Ferring B.V. | Fast disintegrating pharmaceutical composition |
| CN107441068B (en) * | 2017-08-24 | 2021-02-26 | 正大制药（青岛）有限公司 | Clonidine hydrochloride oral film and preparation method thereof |
| CN108272776B (en) * | 2018-04-11 | 2020-12-08 | 苏州大学 | Amitriptyline hydrochloride oral instant film agent |
| CN108272777A (en) * | 2018-04-12 | 2018-07-13 | 天津双硕医药科技有限公司 | A kind of solid composite medicament containing Repaglinide |
| CN108553451A (en) * | 2018-05-23 | 2018-09-21 | 戴铭骏 | A kind of instant film of cefixime oral and preparation method thereof |
| CN109820821B (en) * | 2019-03-29 | 2020-03-27 | 牡丹江医学院 | Oral care solution capable of effectively inhibiting bacteria |
| CN110354106B (en) * | 2019-08-21 | 2023-03-24 | 成都诺和晟泰生物科技有限公司 | Film agent capable of being rapidly dissolved in oral cavity and preparation method thereof |
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| CN102526695A (en) * | 2012-01-05 | 2012-07-04 | 苏州人本药业有限公司 | Application of naja atra venin to treatment of diabetes and diabetic nephropathy complicating disease |
| CN102824333B (en) * | 2012-09-26 | 2014-05-14 | 苏州大学 | Oral quick-dissolving film preparation and preparation method thereof |
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