CN103211801A - Film agent quickly dissolved in oral cavity and preparation method thereof - Google Patents
Film agent quickly dissolved in oral cavity and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a film agent quickly dissolved in the oral cavity and a preparation method thereof. The film agent consists of the following components in percentage by weight: 0.1 to 70 percent of medicinal active ingredients, 30 to 90 percent of water-soluble film forming material, 2 to 20 percent of plasticizer, 0 to 5 percent of disintegrating agent, and 1 to 20 percent of water, wherein the medicinal active ingredients are selected from modified or non-modified cobra venom, sumatriptan succinate, ergotamine dihydrogen tartrate and lomerizine hydrochloride or flunarizine hydrochloride. The film agent is quick in response, and avoids decomposition in gastrointestinal tracts due to oral administration to reduce the treatment effect. The preparation method is simple, economic and practical, and facilitates industrialized batch production.
Description
Technical field
The present invention relates to pharmaceutical technology field, and in particular to one kind treats 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, recurrent exerbation, and very harmful common disease, due to most of etiology unknown, is treated relatively difficult.Wherein rheumatism（Rheumatoid）Property arthritic rate it is high, recurrent exerbation can cause joint deformity, influence function, disability.Simple physical processing has been carried out to chinese cobra venom, it can reach the purpose of attenuation synergistic, modified cobra venom has suppresses inflammation well, pain and the effect and the treatment arthritic effect of Freund's adjuvant of immune response, available for treatment rheumatoid arthritis, the diseases such as systemic loupus erythematosus, and once a day oral administration can produce curative effect, immunosuppressive action intensity is quite or better than Tripterygium wilfordii glycosid, but there is no obvious toxic-side effects under therapeutic dose and cobra venom is to thymus gland, the immune organs such as spleen do not influence, cobra venom suppresses the generation of proinflammatory cytokine, but do not suppress the cell factor of anti-inflammatory.90% is protein in cobra-venom freeze-dried powder, although have good pharmacological action, but lacks rationally effective formulation at present.Oral instant medicine film provides an ideal method of administration, because the permeability of oral mucosa is good, snake venom oral administration makes snake venom active ingredient in buccal absorption, it is possible to reduce decomposition of the gastrointestinal proteases to snake venom active ingredient, improves drug effect and easy to use.
Antimigraine is the periodical attack disease that a class has family morbidity tendency, shows as paroxysmal inclined side pulsatile headache, with Nausea and vomiting and photophobia, is fallen ill again after one section of phase of having a rest.In quiet, dark surrounds or after sleep, headache relief., can be with psychoneural dysfunction when preceding or breaking-out occurs for headache.It is 732.1/ in the incidence of Chinese antimigraine（100000）People, American-European countries's incidence of disease is 1500~2000/（100000）People.The World Health Organization（WHO）Propose, antimigraine turns into the chronic functional obstacle disease of most serious with quadriplegia, phrenoblabia and dementia, be to have a strong impact on patient work and one of common chronic disease of living.Therefore, the prevention and treatment of antimigraine is of increased attention.
The intractable migraine headache of recurrent exerbation, generally can not be alleviated by general treat-and-release.Patient is in addition to lasting progressivity headache, also a series of physiology and affective symptom, such as nausea,vomiting,diarrhea, dehydration, depression, desperate even introgression, it can be controlled by medicines such as Sumatriptan Succinate, Dihydroergotamitie Tartrate, lomerizine hydrochloride, flunarizine hydrochlorides, then implement long-term preventive medicine treatment.Wherein, lomerizine hydrochloride（Lomerizine hydrochloride, Lom）It is the new antimigraine developed jointly by Kanebo and Pharmacia ＆ Upjohn companies, 1999 first in Japan's listing.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 preferable, and the relatively low new drug of side effect.
Said medicine shows preferable therapeutic effect in terms of pain is treated.But treatment pain class medicine, is tablet mostly at present, the formulation such as capsule.In place of formulation such as oral disnitegration tablet, sublingual tablet, dispersible tablet etc. for acute disease medicine come with some shortcomings, special freeze-drier such as need to be used using desivac production, most of oral disnitegration tablets have the shortcomings that friability is big, are made troubles to the packaging of tablet, transport and patient medication.Compared with above-mentioned formulation, oral instant membrane preparation technology is simple, no friability, and preparation prescription easy to carry and proposed by the invention is there is not yet document report.
The content of the invention
First purpose of the present invention is that there is provided a kind of novel thin film preparation for quickly dissolving and absorbing in the oral cavity for treating autoimmune disease, chronic ache, antimigraine.
Second object of the present invention be there is provided it is a kind of treat autoimmune disease, chronic ache, the novel thin film for quickly dissolving and absorbing in the oral cavity of antimigraine preparation method.
To achieve the above object of the invention, the technical solution adopted by the present invention is：A kind of film rapidly-soluble in the oral cavity, by weight, the 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%；Disintegrant, 0~5%；Water, 1~20%；
The medicament active composition is selected from modified or unmodified cobra-venom, Sumatriptan Succinate, Dihydroergotamitie Tartrate, lomerizine hydrochloride or flunarizine hydrochloride.
In above-mentioned technical proposal, the water soluble film-forming material is selected from HPMC, maltodextrin, polyvinyl alcohol, sodium carboxymethylcellulose, gelatin, hyaluronic acid, polyvinylpyrrolidone, one kind or mixture in chitosan, ethyl cellulose, cellulose acetate.
The water soluble film-forming material is the mixture of HPMC and hyaluronic acid, and hydroxypropyl methyl cellulose and hyaluronic acid weight weight ratio are 20~80: 1, the hydroxypropyl methyl cellulose for the centipoise of viscosity 2~50 of described hydroxypropyl methyl cellulose.
It is preferred that technical scheme, hydroxypropyl methyl cellulose and hyaluronic acid weight weight ratio are 50~70: 1, the hydroxypropyl methyl cellulose for the centipoise of viscosity 5~15 of described hydroxypropyl methyl cellulose.
Described plasticizer is selected from one kind or mixture in propane diols, polyethylene glycol 400, glycerine, triethyl citrate；Described disintegrant is selected from one kind or mixture in PVPP, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, pregelatinized starch.
The preparation method of rapidly-soluble film, comprises the following steps in the oral cavity：
1）Water soluble ingredient in addition to water-soluble polymer is soluble in water, obtain the aqueous solution；
2）The biological acceptable water-soluble polymer of at least one is added in the aqueous solution under stirring, is sufficiently stirred for disperseing to obtain polymer gel；
3）Plasticizer is added in above-mentioned polymer gel and is stirred；
4）Add active component and other components and stir；
5）Degassing, polymer gel is spread evenly across on flat board；
6）Blast heating is dried, and heat drying temperature is 40-60 DEG C, and cutting obtains oral quick-dissolving film preparation.
Because above-mentioned technical proposal is used, the present invention has following advantages compared with prior art：
The physiology that the present invention is provided is subjected to film, and medicine is discharged in the oral cavity, rapidly by buccal absorption, is a kind of optimal approach of rapid-action administration for emergency patients.It is particularly suitable for adhering and is rapidly dissolved in the oral cavity of user.Quick dissolving films, release of therapeutic agents, and direct oral cavity mucous membrane quickly absorb pharmaceutically active substances to play drug effect, for pain class disease, and it is significantly the characteristics of also embodying this one dosage type low temperature to shorten the Principle of Pain time.For biopharmaceutical macromolecular drug, drag residence is absorbed in oral mucosa, it is to avoid is orally decomposed and is lessened the curative effect by intestines and stomach.The preparation technology is simple, economical, practical, and is easy to implement industrialization batch production.
Brief description of the drawings
Fig. 1 is that the influence that Dichlorodiphenyl Acetate induced pain after 3h licks the sufficient time is administered in Chinese cobra venom oral instant membrane；
Fig. 2 is that the influence for licking the sufficient time to the pain mouse caused by hot plate after 3h is administered in Chinese cobra venom oral instant membrane；
Fig. 3 is that the influence that PARA FORMALDEHYDE PRILLS(91,95) after 3h causes scorching induced pain to lick the sufficient time is administered in Chinese cobra venom；
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.
Embodiment
Below in conjunction with the accompanying drawings and embodiment the invention will be further described：
Embodiment 1：
Oral instant membrane disintegration time mensuration method：
100mL distilled water is put into 100mL beakers and is placed on magnetic stirrer, 37 DEG C of waters bath with thermostatic control, speed of agitator 50r/min appoints film 10 of getting it filled（1cm×1cm）, one is taken every time, test film is clipped in be put into water-bath on clip starts timing.The record film broken time is the disintegration time limited of film.
Embodiment 2：
Oral instant membrane Measuring Mechanical Properties method：
Using universal material experiment instrument（Instron 3365）, film is cut to the cm sizes of about 2 cm × 0.5（Balanced one week under 43%RH humidity）, the mmmin of draw speed 5-1, every film is all longitudinally stretched, untill film is broken.The mechanical performance of oral instant membrane such as elastic modelling quantity (EM), being calculated as follows for extension percentage (E%) is described.Its Elastic Modulus refers to that in elastic deformation stage the ratio of applied stress and adaptability to changes can use following formula to be calculated：
Elastic modelling quantity=applied stress/adaptability to changes/cross-sectional area
Extension percentage is calculated by following formula：
Extend percentage=length at break-the original length/the original length × 100
Embodiment 3：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 3g |
| Glycerine | 0.3 mL |
| Active component | In right amount |
| Purified water | 15mL |
Specific operation process：By hydroxypropyl methyl cellulose（5 centipoises）Purified water is dispersed under agitation, it is fully dispersed to dissolve to obtain gel, add recipe quantity glycerine, active component is added under stirring, fully dispersed, above-mentioned gel is used automatic coating machine by degassing, it is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.The film is transparent, in light yellow, and demoulding performance is good, and pliability is general.Disintegration time limited is 92s.
Embodiment 4：
| Component | Content |
| Polyvinyl alcohol | 1.2g |
| Glycerine | 0.3 mL |
| Active component | In right amount |
| Purified water | 15mL |
Specific operation process：Polyvinyl alcohol is dispersed in purified water under agitation, fully dispersed to dissolve to obtain gel, and active component is added under stirring, add recipe quantity glycerine, fully dispersed, above-mentioned gel is used automatic coating machine by degassing, it is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.The film is transparent, in light yellow, and demoulding performance is good, and pliability is good, and viscosity is big.Disintegration time limited is 42s.
Embodiment 5：
| Component | Content |
| Polyvinyl alcohol | 1.0g |
| Hyaluronic acid | 0.02g |
| Glycerine | 0.3 mL |
| Active component | In right amount |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, polyvinyl alcohol is added to above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity glycerine is added, active component is added under stirring, it is fully dispersed, degassing, above-mentioned gel is used into 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.The film is transparent, in light yellow, and demoulding performance is good, and pliability is good, and viscosity is big.Disintegration time limited is 31s.
Embodiment 6：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 1.2g |
| Hyaluronic acid | 0.02g |
| Glycerine | 0.3 mL |
| Active component | In right amount |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (5 centipoise) is added into above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity glycerine is added, active component is added under stirring, it is fully dispersed, degassing, above-mentioned gel is used into 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.The film is transparent, in light yellow, and demoulding performance is good, and pliability is good.Disintegration time limited is 47s.
Embodiment 7：
| Component | Content |
| Hydroxypropyl methyl cellulose (15 centipoise) | 0.8 g |
| Hyaluronic acid | 0.02g |
| Glycerine | 0.3 mL |
| Active component | In right amount |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (15 centipoise) is added into above-mentioned solution under agitation, recipe quantity glycerine is added, it is fully dispersed to dissolve to obtain gel, active component is added under stirring, it is fully dispersed, degassing, above-mentioned gel is used into 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.The film is transparent, in light yellow, and demoulding performance is good, and pliability is good.Disintegration time limited is 47s.
Embodiment 8：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Glycerine | 0.3 mL |
| Active component | In right amount |
| Sodium carboxymethyl starch | 0.02g |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (5 centipoise) is added into above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity glycerine is added, active component, sodium carboxymethyl starch are added under stirring, fully dispersed, above-mentioned gel is used automatic coating machine by degassing, it is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.The film is transparent, in light yellow, and demoulding performance is good, and pliability is general.Disintegration time limited is 18s.
Embodiment 9：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Glycerine | 0.3 mL |
| Active component | In right amount |
| Low-substituted hydroxypropyl cellulose | 0.02g |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (5 centipoise) is added into above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity glycerine is added, active component, low-substituted hydroxypropyl cellulose are added under stirring, fully dispersed, above-mentioned gel is used automatic coating machine by degassing, it is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.The film is transparent, in light yellow, and demoulding performance is good, and pliability is good.Disintegration time limited is 27s.
Embodiment 10：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Glycerine | 0.3 mL |
| Active component | In right amount |
| PVPP | 0.02g |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (5 centipoise) is added into above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity glycerine is added, active component, PVPP are added under stirring, fully dispersed, above-mentioned gel is used automatic coating machine by degassing, it is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.The film is transparent, in light yellow, and demoulding performance is good, and pliability is good.Disintegration time limited is 22s.
Embodiment 11：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Glycerine | 0.3 mL |
| Active component | In right amount |
| Pregelatinized starch | 0.02g |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (5 centipoise) is added into above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity glycerine is added, active component, pregelatinized starch are added under stirring, fully dispersed, above-mentioned gel is used automatic coating machine by degassing, it is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.The film is transparent, in light yellow, and demoulding performance is good, and pliability is good.Disintegration time limited is 22s.
Embodiment 12：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Propane diols | 0.3 mL |
| Active component | In right amount |
| Pregelatinized starch | 0.02g |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (5 centipoise) is added into above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity propane diols is added, active component, pregelatinized starch are added under stirring, fully dispersed, above-mentioned gel is used automatic coating machine by degassing, it is spread evenly across on flat board, air blast, heat drying, heating-up temperature is 60 DEG C, cutting, obtains oral instant membrane.The film is transparent, in light yellow, and demoulding performance is good, and pliability is general.Disintegration time limited is 25s.
Embodiment 13：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Propane diols | 0.3 mL |
| Polyethylene glycol 400 | 0.3mL |
| Active component | In right amount |
| Pregelatinized starch | 0.02g |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (5 centipoise) is added into above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity propane diols is added, polyethylene glycol 400 adds active component under stirring, pregelatinized starch, fully dispersed, degassing, above-mentioned gel is used into 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.The film is transparent, in light yellow, and demoulding performance is good, and pliability is good.Disintegration time limited is 26s.
Embodiment 14：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 1.2 g |
| Hyaluronic acid | 0.02g |
| Propane diols | 0.3 mL |
| Triethyl citrate | 0.3mL |
| Active component | In right amount |
| Pregelatinized starch | 0.02g |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (5 centipoise) is added into above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity propane diols is added, triethyl citrate adds active component under stirring, pregelatinized starch, fully dispersed, degassing, above-mentioned gel is used into 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.The film is transparent, in light yellow, and demoulding performance is good, and pliability is general.Disintegration time limited is 30s.
Embodiment 15：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 0.8 g |
| Hyaluronic acid | 0.02g |
| Propane diols | 0.3 mL |
| Polyethylene glycol 400 | 0.3mL |
| Active component | In right amount |
| Pregelatinized starch | 0.02g |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (5 centipoise) is added into above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity propane diols is added, pregelatinized starch adds active component under stirring, pregelatinized starch, fully dispersed, degassing, above-mentioned gel is used into 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.The film is transparent, in light yellow, and demoulding performance is good, and pliability is general, easy friability.Disintegration time limited is 18s.
Embodiment 16：
| Component | Content |
| Hydroxypropyl methyl cellulose (5 centipoise) | 1.6 g |
| Hyaluronic acid | 0.04g |
| Propane diols | 0.3 mL |
| Polyethylene glycol 400 | 0.3mL |
| Active component | In right amount |
| Pregelatinized starch | 0.02g |
| Purified water | 15mL |
Specific operation process：Hyaluronic acid is scattered in purified water under agitation and dissolved, hydroxypropyl methyl cellulose (5 centipoise) is added into above-mentioned solution under agitation, it is fully dispersed to dissolve to obtain gel, recipe quantity propane diols is added, triethyl citrate adds active component under stirring, pregelatinized starch, fully dispersed, degassing, above-mentioned gel is used into 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.The film is transparent, in light yellow, and demoulding performance is good, and pliability is general.Disintegration time limited is 28s.
Embodiment 17：
1 Chinese cobra venom oral instant medicine film suppresses pain reaction caused by acetic acid：
Acetic acid writhing test is the experimental method for commonly using classical screening Acute Pain antalgesic.Because the experimental implementation is simple, therefore it is the common model of evaluation and screening antalgesic.ICR mouse are randomly divided into 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（10μg/kg）, middle dose group（30 μg/kg）, heavy dose of group（90 μg/kg）, aspirin（100mg/kg）, Chinese cobra venom oral instant membrane oral cavity is buccal, saline control group and aspirin gastric infusion, 1 time a day, continuous 5 days, after last dose 3h, injected with 0.8% acetum abdominal cavity, every mouse 0.2ml, each mouse writhing number of times in 15min after record injection.Snake venom heavy dose significantly reduces the inflammatory pain caused by acetic acid, better than in snake venom, low dosage.As a result see that the influence that PARA FORMALDEHYDE PRILLS(91,95) after 3h causes scorching induced pain to add the sufficient time is administered for Chinese cobra venom oral instant membrane in Fig. 3（ 
± SD, n=11-12）；The * P compared with control group<0.05, * * P<0.01.
2 Chinese cobra venom oral instant medicine films suppress pain reaction caused by hot plate：
Hot plate method equipment is simple, easy to use, and clearly, small to tissue loss, latency of pain response is longer, is easy to observe and measures smaller difference between medicine for observation index, comparative drug analgesic activity power, speed and duration.KM mouse are randomly divided into 5 groups (n=10) female half and half, body weight 18-22g：Saline control group, Chinese cobra venom oral instant membrane small dose group（10μg/kg）, middle dose group（30 μg/kg）, heavy dose of group（90 μg/kg）, morphine（5mg/kg）, morphine positive controls are in experiment same day abdominal cavity injection 1 time（0.1ml/10g）, Chinese cobra venom oral instant membrane oral cavity is buccal, saline control group gastric infusion, and 1 time a day, continuous 5 days, 30min, 3h, 6h, 9h determined pain threshold respectively after last dose.What snake venom middle dosage and heavy dose of snake venom significantly reduced the pain mouse caused by hot plate adds the sufficient time, better than snake venom low dosage, and when 6h, there is significant difference compared with control group.As a result see that the influence for adding the sufficient time after 3h to the pain mouse caused by hot plate is administered for Chinese cobra venom oral instant membrane by Fig. 4（
± SD, n=10）；The * P compared with control group<0.05, * * P<0.01.
3 Chinese cobra venom oral instant medicine films suppress formaldehyde-caused pain reaction：
Formaldehyde causes the valid model that inflammatory pain model is constant pain caused by chemical noxious stimulation, is widely used in the research of Theory of Pain Mechanism and the screening of antalgesic.KM mouse are randomly divided into 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 μg/kg）, middle dose group（30 μg/kg）, heavy dose of group（90 μg/kg）, aspirin（100mg/kg）Chinese cobra venom oral instant membrane oral cavity is buccal, saline control group and aspirin gastric infusion, 1 time a day, continuous 5 days, after last dose 3h, the μ l induced pains of 1.5% formalin 20 are subcutaneously injected in right side of mice vola, put back to immediately in transparent observing container, record mouse respectively with timer and add the sufficient time（Second）, record two phases.Ith phase is 0~5min after induced pain for acute stage, and the IIth phase is 15~30min after induced pain for the tetanic phase.What snake venom middle dosage and heavy dose of snake venom significantly reduced the inflammatory pain mouse caused by formaldehyde adds the sufficient time, better than snake venom low dosage.As a result see that the influence that PARA FORMALDEHYDE PRILLS(91,95) after 3h causes scorching induced pain to add the sufficient time is administered for Chinese cobra venom in Fig. 5（
± SD, n=11-12）；The * P compared with control group<0.05, * * P<0.01, * * * P<0.001.
Claims (6)
1. a kind of film rapidly-soluble in the oral cavity, it is characterised in that by weight, the 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%；Disintegrant, 0~5%；Water, 1~20%；
The medicament active composition is selected from modified or unmodified cobra-venom, Sumatriptan Succinate, Dihydroergotamitie Tartrate, lomerizine hydrochloride or flunarizine hydrochloride.
2. film rapidly-soluble in the oral cavity according to claim 1, it is characterised in that：The water soluble film-forming material is selected from one kind or mixture in HPMC, maltodextrin, polyvinyl alcohol, sodium carboxymethylcellulose, gelatin, hyaluronic acid, polyvinylpyrrolidone, chitosan, ethyl cellulose, cellulose acetate.
3. film rapidly-soluble in the oral cavity according to claim 2, it is characterised in that：The water soluble film-forming material is the mixture of HPMC and hyaluronic acid, and hydroxypropyl methyl cellulose and hyaluronic acid weight weight ratio are 20~80: 1, the hydroxypropyl methyl cellulose for the centipoise of viscosity 2~50 of described hydroxypropyl methyl cellulose.
4. film rapidly-soluble in the oral cavity according to claim 3, it is characterised in that：Hydroxypropyl methyl cellulose and hyaluronic acid weight weight ratio are 50~70: 1, the hydroxypropyl methyl cellulose for the centipoise of viscosity 5~15 of described hydroxypropyl methyl cellulose.
5. film rapidly-soluble in the oral cavity according to claim 1, it is characterised in that：Described plasticizer is selected from one kind or mixture in propane diols, polyethylene glycol 400, glycerine, triethyl citrate；Described disintegrant is selected from one kind or mixture in PVPP, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, pregelatinized starch.
6. the preparation method of any film rapidly-soluble in the oral cavity in claim 1 to 5, it is characterised in that comprise the following steps：
1）Water soluble ingredient in addition to water-soluble polymer is soluble in water, obtain the aqueous solution；
2）The biological acceptable water-soluble polymer of at least one is added in the aqueous solution under stirring, is sufficiently stirred for disperseing to obtain polymer gel；
3）Plasticizer is added in above-mentioned polymer gel and is stirred；
4）Add active component and other components and stir；
5）Degassing, polymer gel is spread evenly across on flat board；
6）Blast heating is dried, and heat drying temperature is 40-60 DEG C, and cutting obtains oral quick-dissolving film preparation.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107441068A (en) * | 2017-08-24 | 2017-12-08 | 青岛正大海尔制药有限公司 | A kind of clonidine hydrochloride pelliculae pro cavo oris and preparation method thereof |
| CN108272776A (en) * | 2018-04-11 | 2018-07-13 | 苏州大学 | Amitriptyline Hydrochloride oral quick-dissolving film preparation |
| 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 |
| CN109820821A (en) * | 2019-03-29 | 2019-05-31 | 牡丹江医学院 | A kind of effectively antibacterial oral cavity conditioning liquid |
| CN110354106A (en) * | 2019-08-21 | 2019-10-22 | 成都诺和晟泰生物科技有限公司 | A kind of film rapidly-soluble in the oral cavity and preparation method thereof |
| US10952959B2 (en) | 2017-01-11 | 2021-03-23 | Ferring B.V. | Fast disintegrating pharmaceutical composition |
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| CN102824333A (en) * | 2012-09-26 | 2012-12-19 | 苏州大学 | Oral quick-dissolving film preparation and preparation method thereof |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10952959B2 (en) | 2017-01-11 | 2021-03-23 | Ferring B.V. | Fast disintegrating pharmaceutical composition |
| CN107441068A (en) * | 2017-08-24 | 2017-12-08 | 青岛正大海尔制药有限公司 | A kind of clonidine hydrochloride pelliculae pro cavo oris and preparation method thereof |
| 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 |
| CN108272776A (en) * | 2018-04-11 | 2018-07-13 | 苏州大学 | Amitriptyline Hydrochloride oral quick-dissolving film preparation |
| 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 |
| CN109820821A (en) * | 2019-03-29 | 2019-05-31 | 牡丹江医学院 | A kind of effectively antibacterial oral cavity conditioning liquid |
| CN110354106A (en) * | 2019-08-21 | 2019-10-22 | 成都诺和晟泰生物科技有限公司 | A kind of film rapidly-soluble in the oral cavity and preparation method thereof |
| 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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