CN105641103A - Preparation method and application of medicament for treating insomnia and gel thereof - Google Patents
Preparation method and application of medicament for treating insomnia and gel thereof Download PDFInfo
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- CN105641103A CN105641103A CN201610008716.5A CN201610008716A CN105641103A CN 105641103 A CN105641103 A CN 105641103A CN 201610008716 A CN201610008716 A CN 201610008716A CN 105641103 A CN105641103 A CN 105641103A
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- medicament
- phosphate buffer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
- A61K36/725—Ziziphus, e.g. jujube
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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Abstract
The invention discloses a medicament for treating insomnia and a preparation method and application thereof. The medicament for treating insomnia is composed of the following components in mass percent: 2-6% of jujuboside extract, 16-22% of poloxamer P407, 1-6% of poloxamer P188, 6-12% of PEG400, 0.01-0.03% of nipagin and balance of phosphate buffer solution, wherein the sum of the mass percents is 100%. The medicament for treating insomnia disclosed by the invention adopts a temperature-sensitive gel as a dosage form of jujuboside, thus after the medicament is dripped in liquid form into the nasal cavity, the medicament can flow onto mucous membrane in the deeper olfactory region where the brain bioavailability is verified high for administration; the medicament changes into semi-solid with a biological adhesion action in the nasal cavity, thereby continuously attaching to the mucous membrane in the olfactory region, solving the problem that the traditional dosage form is liable to lose and result in lower bioavailability and transient administration, and improving the sleeping quality of patients continuously.
Description
Technical field
The invention belongs to technical field of medicine, be specifically related to a kind of medicine treating insomnia, the invention still further relates to the preparation method and application of this medicament gelling agent.
Background technology
At present, continuous aggravation along with social pressure, the insomnia size of population and speedup hit new peak repeatly, the trend of have a sleepless night oriented Age Variations level and the development of many social class, and even traditional society thinks that sleep good child, group of college students also occur in that substantial amounts of insomnia problem. In the symptom of puzzlement insomniac, except difficulty falling asleep, still there are the problems such as sleep awakening shallow, easy, poor sleeping quality. The drug main for the treatment of insomnia at present to have Benzodiazepines such as the chemicalses such as stable, alprazolam, lorazepam etc., barbiturates such as phenobarbital, other class such as zolpidem. The type medicine common problem is in that dependency additive problem even, in use often because of produce dependency cannot drug withdrawal, but need to continue to increase dosage because producing problem of resistance, cause that many patients are in a dilemma, agonizing.
At present, the medicine of another kind for the treatment of insomnia is various Chinese patent medicine compound preparations, and wherein common component is Semen Ziziphi Spinosae. In Semen Ziziphi Spinosae, the effective ingredient of calming soporific is jujuboside, and saponin component molecular polarity is very big, it is difficult to enters blood through blood brain barrier by oral absorption, there is pharmacokinetics problem urgently to be resolved hurrily. Therefore, often there is the problem that clinical efficacy is unstable in the oral Chinese patent medicine of the type.
Summary of the invention
It is an object of the invention to provide a kind of medicine treating insomnia, being difficult to of solving that the medicine of existing treatment insomnia exists that dependency addicted problem even and Chinese patent medicine compound preparation exist enters the blood problem through blood brain barrier by oral absorption.
The preparation method that it is a further object to provide a kind of medicament gelling agent treating insomnia.
3rd purpose of the present invention is to provide the application of a kind of said medicine gel.
First technical scheme of the present invention is, a kind of medicine treating insomnia, composed of the following components by mass percentage: jujuboside extract 2%��6%, F127 16%��22%, F68 1%��6%, PEG4006%��12%, nipalgin 0.01%��0.03%, all the other are phosphate buffer, and above-mentioned mass percent sum is 100%.
Second technical scheme of the present invention is, the preparation method of a kind of medicament gelling agent treating insomnia, specifically implements according to following steps:
Step 1, weigh respectively by mass percentage: jujuboside extract 2%��6%, F127 16%��22%, F68 1%��6%, PEG4006%��12%, nipalgin 0.01%��0.03%, all the other are phosphate buffer, and above-mentioned mass percent sum is 100%;
Step 2, take portion phosphate buffer, add jujuboside extract, dissolve in rearmounted ice-water bath, be slowly added to F127, F68, PEG400 and nipalgin under magnetic stirring, add remaining phosphate buffer, put into after uniform wet in 4��10 DEG C of refrigerators and place 12��48 hours, making that gel is fully swelling to be uniformly dispersed, until obtaining clear and bright solution, obtaining final product.
The feature of the present invention also resides in,
Phosphate buffer obtains in the following manner: adds sodium hydroxide solution, dilute with water in potassium dihydrogen phosphate, shakes up, regulates pH=6��7 and get final product.
The present invention is the 3rd technical scheme adopted, the application of the medicament gelling agent of above-mentioned preparation, by instilling the nasal cavity treatment for tranquillizing and allaying excitement and insomnia.
The feature of the present invention also resides in,
After this medicament gelling agent enters nasal cavity, regio olfactoria mucosa being supported with liquid flow, and because heating up, phase in version occur, continuing to play a role thus being attached to bronchia mucosal.
The invention has the beneficial effects as follows, the present invention treats the medicine of insomnia, it it is a kind of jujuboside nasal cavity site-specific delivery of drugs thermosensitive hydrogel, adopt thermosensitive hydrogel as the form of administration of jujuboside, make it: 1. after instilling nasal cavity in liquid form, deeper regio olfactoria mucosa can being flowed into, having been found to be directed through blood brain barrier and brain bioavailability height at this regional administration, thus solving effective ingredient jujuboside in conventional oral Semen Ziziphi Spinosae preparation to be difficult to the problem by blood brain barrier; 2. making medicament heat up owing to body temperature is higher relative to room temperature, medicine of the present invention at nasal cavity generation phase in version, can be become non-chemically to cross-link semi-solid gel by liquid conversion, be attached to nasal mucosa, thus having longer administration time to improve bioavailability; 3. it is changed into the semisolid with bio-adhesive effect at nasal cavity, solves the drawback that tradition form of nose drops is prone to loss and causes the relatively low and transient administration of bioavailability the sleep quality of constantly improve patient.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is described in detail.
A kind of medicine treating insomnia of the present invention, composed of the following components by mass percentage: jujuboside extract 2%��6%, F127 16%��22%, F68 1%��6%, PEG4006%��12%, nipalgin 0.01%��0.03%, all the other are phosphate buffer, and above-mentioned mass percent sum is 100%.
Phosphate buffer obtains in the following manner: adds sodium hydroxide solution, dilute with water in potassium dihydrogen phosphate, shakes up, regulates pH=6��7 and get final product.
In medicine of the present invention, jujuboside extract is principal agent; F127 is gel-type vehicle; F68 and PEG400 regulate for gelling temp, and PEG400 is wetting agent; Nipalgin is antibacterial.
Usage and dosage
Usage: collunarium, sleeps use in first 20 minutes.
Consumption: 1��2 droplet/time, 1��2 times/day.
The preparation method of the medicament gelling agent of above-mentioned treatment insomnia, specifically implements according to following steps:
Step 1, weigh respectively by mass percentage: jujuboside extract 2%��6%, F127 16%��22%, F68 1%��6%, PEG4006%��12%, nipalgin 0.01%��0.03%, all the other are phosphate buffer, and above-mentioned mass percent sum is 100%;
Step 2, take portion phosphate buffer, add jujuboside extract, dissolve in rearmounted ice-water bath, be slowly added to F127, F68, PEG400 and nipalgin under magnetic stirring, add remaining phosphate buffer, put into after uniform wet in 4��10 DEG C of refrigerators and place 12��48 hours, making that gel is fully swelling to be uniformly dispersed, until obtaining clear and bright solution, obtaining final product.
(1) determination experiment of gelation temperature (Tgel):
Adopt " stirrer method ": the gelation temperature (Tgel) of 3 groups of medicines of the present invention of parallel assay, method particularly includes: in 50ml small beaker, add a certain amount of medicine of the present invention respectively, be placed in ice-water bath. Inserting, by beaker sealing and in centre punching, the thermometer that precision is 0.1 DEG C, place stirrer simultaneously, the mercury ball of thermometer submerges in thermosensitive hydrogel liquid completely. Then it is placed in the water-bath of heat collecting type constant-temperature heating magnetic stirring apparatus, adjustment speed of agitator is 200r/min, water-bath is kept slowly to heat up with the speed of 1-2 DEG C/min, temperature when magnetic stir bar being stopped operating is designated as gelation temperature, the measurement result of three groups is as follows: 1. 33.0 DEG C, 2. 33.5 DEG C, 3. 33.0 DEG C, and average gelation temperature is 33.1 DEG C.
(2) pharmacodynamic experiment
1. laboratory animal
Healthy SD rat 40, male and female half and half, body weight 180-220g, is bought by Xi'an Communications University's Experimental Animal Center. Every rat is all raised under the same conditions, freely drinks water, ingests, and keeps natural lighting.
2. experimental drug
The jujuboside phosphate buffer that positive controls uses, means and dissolves jujuboside with phosphate buffer (pH=6��7) 20 times amount, stand-by; Fenclonine (para-chlorophenylalanine, PCPA): purchased from Aladdin Reagent Company.
3. experiment packet
By randomly assigne, being divided into four groups, often group 10, A group is blank group, and B group is PCBA model group, and C group is positive controls, and D group is experimental group.
4. the foundation of insomnic rats model
B, C, D group rat gives disposable celiac injection PCPA300mg/kg. A group rat gives the lumbar injection normal saline with dosage.
5. administration
C group gives jujuboside phosphate buffer (100 �� l/d) and instills nasal cavity, every day 1 time, successive administration 7 days; D group gives the present invention (100 �� l/d) and instills nasal cavity, and administering mode, time are with C group; A group, B component do not instill nasal cavity (100 �� l/d) with normal saline, and administering mode, time are with C group.
6. observe the present invention impact on rat spontaneous activity
After giving PCPA24 hour, before first time administration, rat is put in the raising box of receptacle, after adapting to 3min, observe the spontaneous activity situation of each Mus respectively, including the free activity time in 2min and the liftoff act of forelimb vertical number of times. Again observed and recorded These parameters after last administration 60min and after 90min.
7. result
The pharmaceutical research effect data of table 1 present invention
8. conclusion
Conclusion shows that D group (collunarium group of the present invention) can reduce rat central excitatory (P < 0.05) under PCPA stimulates compared to B, C group.Owing to this model is widely recognized as in sedative hypnotics research field, it is believed that the present invention has definite sedative-hypnotic property, especially the present invention is compared to C group, the effect of the positive controls namely directly giving the jujuboside phosphate buffer without nasal cavity site-specific delivery of drugs effect to be got well, and has significant difference.
Embodiment 1
Step 1, weighs by mass percentage respectively: jujuboside extract 2%, F127 20%, F68 4%, PEG40012%, nipalgin 0.01%, and all the other are phosphate buffer, and above-mentioned mass percent sum is 100%;
Step 2, take portion phosphate buffer, add jujuboside extract, dissolve in rearmounted ice-water bath, be slowly added to F127, F68, PEG400 and nipalgin under magnetic stirring, add remaining phosphate buffer, put into after uniform wet in 4 DEG C of refrigerators and place 48 hours, making that gel is fully swelling to be uniformly dispersed, until obtaining clear and bright solution, obtaining final product.
Embodiment 2
Step 1, weighs by mass percentage respectively: jujuboside extract 4%, F127 22%, F68 6%, PEG4006%, nipalgin 0.02%, and all the other are phosphate buffer, and above-mentioned mass percent sum is 100%;
Step 2, take portion phosphate buffer, add jujuboside extract, dissolve in rearmounted ice-water bath, be slowly added to F127, F68, PEG400 and nipalgin under magnetic stirring, add remaining phosphate buffer, put into after uniform wet in 8 DEG C of refrigerators and place 36 hours, making that gel is fully swelling to be uniformly dispersed, until obtaining clear and bright solution, obtaining final product.
Embodiment 3
Step 1, weighs by mass percentage respectively: jujuboside extract 6%, F127 16%, F68 1%, PEG4008%, nipalgin 0.03%, and all the other are phosphate buffer, and above-mentioned mass percent sum is 100%;
Step 2, take portion phosphate buffer, add jujuboside extract, dissolve in rearmounted ice-water bath, be slowly added to F127, F68, PEG400 and nipalgin under magnetic stirring, add remaining phosphate buffer, put into after uniform wet in 10 DEG C of refrigerators and place 12 hours, making that gel is fully swelling to be uniformly dispersed, until obtaining clear and bright solution, obtaining final product.
Claims (5)
1. the medicine treating insomnia, it is characterized in that, composed of the following components by mass percentage: jujuboside extract 2%��6%, F127 16%��22%, F68 1%��6%, PEG4006%��12%, nipalgin 0.01%��0.03%, all the other are phosphate buffer, and above-mentioned mass percent sum is 100%.
2. the preparation method of the medicament gelling agent treating insomnia, it is characterised in that specifically implement according to following steps:
Step 1, weigh respectively by mass percentage: jujuboside extract 2%��6%, F127 16%��22%, F68 1%��6%, PEG4006%��12%, nipalgin 0.01%��0.03%, all the other are phosphate buffer, and above-mentioned mass percent sum is 100%;
Step 2, take portion phosphate buffer, add jujuboside extract, dissolve in rearmounted ice-water bath, be slowly added to F127, F68, PEG400 and nipalgin under magnetic stirring, add remaining phosphate buffer, put into after uniform wet in 4��10 DEG C of refrigerators and place 12��48 hours, making that gel is fully swelling to be uniformly dispersed, until obtaining clear and bright solution, obtaining final product.
3. the preparation method of the medicament gelling agent for the treatment of insomnia according to claim 2, it is characterised in that phosphate buffer obtains in the following manner: adds sodium hydroxide solution, dilute with water in potassium dihydrogen phosphate, shakes up, regulates pH=6��7 and get final product.
4. the application of medicament gelling agent prepared by the preparation method according to Claims 2 or 3, it is characterised in that by instilling the nasal cavity treatment for tranquillizing and allaying excitement and insomnia.
5. the application of the medicament gelling agent according to claim 4, it is characterized in that, after it enters nasal cavity, supporting regio olfactoria mucosa with liquid flow, and because heating up, phase in version occur, continuing to play a role thus being attached to bronchia mucosal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610008716.5A CN105641103A (en) | 2016-01-07 | 2016-01-07 | Preparation method and application of medicament for treating insomnia and gel thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610008716.5A CN105641103A (en) | 2016-01-07 | 2016-01-07 | Preparation method and application of medicament for treating insomnia and gel thereof |
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| Publication Number | Publication Date |
|---|---|
| CN105641103A true CN105641103A (en) | 2016-06-08 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610008716.5A Pending CN105641103A (en) | 2016-01-07 | 2016-01-07 | Preparation method and application of medicament for treating insomnia and gel thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113262260A (en) * | 2021-06-05 | 2021-08-17 | 亳州益智健康产业有限公司 | Cold compress gel for treating insomnia |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101053550A (en) * | 2007-04-25 | 2007-10-17 | 昆明制药集团股份有限公司 | Rhizoma Gastrodiae nasal gel preparation |
| CN102349944A (en) * | 2010-06-01 | 2012-02-15 | 四川大千药业有限公司 | Nasal thermosensitive in-situ gel prepared by radix scutellariae extract, its preparation method and its application |
| CN103169649A (en) * | 2013-04-11 | 2013-06-26 | 中国人民解放军总医院 | Temperature and ion dual-sensitive in-situ gel nasal cavity drug delivery system |
-
2016
- 2016-01-07 CN CN201610008716.5A patent/CN105641103A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101053550A (en) * | 2007-04-25 | 2007-10-17 | 昆明制药集团股份有限公司 | Rhizoma Gastrodiae nasal gel preparation |
| CN102349944A (en) * | 2010-06-01 | 2012-02-15 | 四川大千药业有限公司 | Nasal thermosensitive in-situ gel prepared by radix scutellariae extract, its preparation method and its application |
| CN103169649A (en) * | 2013-04-11 | 2013-06-26 | 中国人民解放军总医院 | Temperature and ion dual-sensitive in-situ gel nasal cavity drug delivery system |
Non-Patent Citations (1)
| Title |
|---|
| 樊岚岚: "《《本草纲目》养生全书》", 31 January 2014, 天津科学技术出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113262260A (en) * | 2021-06-05 | 2021-08-17 | 亳州益智健康产业有限公司 | Cold compress gel for treating insomnia |
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Application publication date: 20160608 |
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