CN109316457A - A kind of cyclobenzaprine hydrochloride sustained release preparation and preparation method thereof - Google Patents
A kind of cyclobenzaprine hydrochloride sustained release preparation and preparation method thereof Download PDFInfo
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- CN109316457A CN109316457A CN201811412749.1A CN201811412749A CN109316457A CN 109316457 A CN109316457 A CN 109316457A CN 201811412749 A CN201811412749 A CN 201811412749A CN 109316457 A CN109316457 A CN 109316457A
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- sustained release
- cyclobenzaprine hydrochloride
- release preparation
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
The present invention relates to field of pharmaceutical preparations, and in particular to a kind of cyclobenzaprine hydrochloride sustained release preparation and preparation method thereof.Cyclobenzaprine hydrochloride sustained release preparation of the invention is a kind of clad sheet, and the group of interior chip becomes active ingredient hydrochloric acid cyclobenzaprine and C14H10Cl2NNaO2, sustained release agent, diluent, adhesive, disintegrating agent and lubricant, middle layer is sustained-release coating layer, and the composition of outer layer is identical as interior chip.Clad sheet selective cross-linking sodium alginate of the invention and chitosan are as sustained release agent, select cyclobenzaprine hydrochloride and C14H10Cl2NNaO2 as active constituent, it is found by experiment that, compared with only with the clad sheet of a kind of analgesic bioactive substance cyclobenzaprine hydrochloride or C14H10Cl2NNaO2, the clad sheet that cyclobenzaprine hydrochloride and C14H10Cl2NNaO2 are used in combination is achieved into synergistic function.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to a kind of cyclobenzaprine hydrochloride sustained release preparation and preparation method thereof.
Background technique
Cyclobenzaprine hydrochloride (cyclobenzaprine hydrochloride, 1), the entitled 5~(3~dimethylamino of chemistry
Propylidene) dibenzo [a, d] cycloheptyl pinene hyhrochloride is the muscle relaxant of Merck company of U.S. research and development, on multinational
City, trade name Flexeril.
Cyclobenzaprine hydrochloride is central muscle relaxant, and site of action may not be the resistance of neuromere muscle in brain stem
, there is skeletal muscle relaxation effect, cyclobenzaprine hydrochloride also has cholinolytic effect, can alleviate local muscles in disconnected agent after administration
Spasm symptom, while the normal function of muscle is not interfered, muscle epidemic disease contraction caused by Central nervous systemic disease is invalid.Clinic is main
It is used to treat the adjuvant drug of painful part muscle cramp.
The high sensitiveness of muscle in several animal models can be alleviated or be eliminated to cyclobenzaprine hydrochloride.Zooscopy mentions
Show, cyclobenzaprine hydrochloride is unable to direct interference animal muscle nervous function or directly affects skeletal muscle function, mainly makees
For the brain part of central nervous system, and not directly control muscle cramp and the open-minded flesh of relaxation bone.It prompts on evidence, hydrochloric acid
Cyclobenzaprine reduces abnormalities muscular movement, reaches flesh pine effect by influencing motor fibre.
C14H10Cl2NNaO2 (diclofenac sodium, 1) belongs to the potent non-steroid anti-inflammatory drug of the third generation, it mainly leads to
Inhibition cyclooxygenase is crossed to inhibit arachidonic metabolism, so that the synthesis of prostaglandin and the generation of blood platelet are reduced, with
And inhibit lipoxygenase to a certain extent and reduce the generations of the products such as leukotriene, bradykinin, the especially suppression to leukotriene β 4
Production is with more obvious, by the inhibition to these pro-inflammatory cytokines to play antipyretic-antalgic antiinflammation.C14H10Cl2NNaO2 is controlled
The mechanism for treating neurogenic pain is by inhibiting before highly expressed peroxidase activity is reduced in injured nerve and spinal cord
The generation of column parathyrine, to make Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 (SP) in dorsal root ganglion and cornu dorsale medullae spinalis shallow-layer, calcitonin gene-related peptide (CGRP)
Expression accordingly reduce, and then play analgesic activity.
C14H10Cl2NNaO2 is Arylacetic acids non-steroid antiphlogistic, is widely used in all kinds of chronic bone joint pains, and same
Class drug is compared, and analgesia, anti-inflammatory and refrigeration function are 2~2.5 times stronger than Indomethacin, 26~50 times stronger than aspirin, is
A kind of novel potent anti-inflammatory antalgesic.
But cyclobenzaprine hydrochloride and C14H10Cl2NNaO2 all have that oral absorption is fast, biological half-life is short, it is general
Obstruction-removing prescription type is multiple per medication day by day, and medication is more frequent, affects the compliance of patient medication.There is presently no about hydrochloric acid ring
Benzene pricks woods and C14H10Cl2NNaO2 combines the research for preparing sustained release preparation and report.
Summary of the invention
The object of the present invention is to provide a kind of cyclobenzaprine hydrochloride sustained release preparations and preparation method thereof that analgesic effect is excellent.
The technical solution that the present invention solves the technical problem is a kind of cyclobenzaprine hydrochloride sustained release preparation, is a kind of cored
The group of piece, interior chip becomes active ingredient hydrochloric acid cyclobenzaprine and C14H10Cl2NNaO2, sustained release agent, diluent, adhesive, disintegrating agent
And lubricant, middle layer are sustained-release coating layer, the composition of outer layer is identical as interior chip.
The weight part ratio of cyclobenzaprine hydrochloride and C14H10Cl2NNaO2 is 1~5:1~10 in the clad sheet and outer layer.
The weight ratio of the interior chip and outer layer is 3~9:2~6, preferably 3:2.
The dosage of the sustained-release coating layer is 1%~5%.
The sustained release agent is made of crossslinked sodium alginate and chitosan, and the ratio of the crossslinked sodium alginate and chitosan is
1~10:1~10.
The diluent includes one of microcrystalline cellulose, amylum pregelatinisatum, dextrin, mannitol and sorbierite or more
Kind.
Described adhesive includes in starch slurry, methylcellulose, ethyl cellulose, hydroxypropylcellulose and hydroxypropyl methylcellulose
It is one or more.
The disintegrating agent includes in dried starch, croscarmellose sodium, alginic acid and low-substituted hydroxypropyl cellulose
It is one or more.
The lubricant includes one of talcum powder, magnesium stearate and superfine silica gel powder or a variety of.
In cyclobenzaprine hydrochloride sustained release preparation of the invention in chip and outer layer each component weight are as follows: hydrochloric acid ring
Benzene prick 1~6 part of woods, 1~4 part of C14H10Cl2NNaO2,15~30 parts of diluent, 2~10 parts of adhesive, 10~20 parts of disintegrating agent and profit
0.1~1 part of lubrication prescription.
Invention also provides the preparation methods of above-mentioned cyclobenzaprine hydrochloride sustained release preparation, comprising the following steps:
(1) raw material is weighed by formula rate；
(2) first pressed internal core piece, then be coated, finally suppress clad sheet to get.
Beneficial effects of the present invention:
The present invention provides a kind of clad sheet selective cross-linking seas that completely new cyclobenzaprine hydrochloride cored slice prescription is of the invention
Mosanom and chitosan select cyclobenzaprine hydrochloride and C14H10Cl2NNaO2 as active constituent, are sent out by test as sustained release agent
It is existing, compared with only with the clad sheet of a kind of analgesic bioactive substance cyclobenzaprine hydrochloride or C14H10Cl2NNaO2, hydrochloric acid ring benzene is pricked
The clad sheet that woods and C14H10Cl2NNaO2 are used in combination achieves synergistic function.
Detailed description of the invention
Fig. 1 is cyclobenzaprine hydrochloride clad sheet analgesic effect ag(e)ing test figure
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to conventional strip
Part or according to the normal condition proposed by manufacturer.Unless otherwise stated, otherwise all percentage, ratio, ratio or number is pressed
Poidometer.
Unless otherwise defined, all professional and scientific terms as used herein and meaning familiar to those skilled in the art
Justice is identical.In addition, any method similar to or equal to what is recorded and material can be applied to the method for the present invention.Wen Zhong
The preferred implement methods and materials are for illustrative purposes only.
The preparation of embodiment cyclobenzaprine hydrochloride clad sheet
Cyclobenzaprine hydrochloride clad sheet, first pressed internal core piece are prepared according to the formula (g/ piece) of table 1, then is coated, is finally pressed
Clad sheet processed to get.
1 cyclobenzaprine hydrochloride cored slice prescription of table
Test example cyclobenzaprine hydrochloride clad sheet hot plate method in mice analgesic effect ag(e)ing test
Kunming kind female mice is placed on (55 ± 1) DEG C hot plate pain threshold detector, is clocked at once, until occurring licking metapedes for the first time
Or stopping timing when stamping metapedes, the gained time is the basic threshold of pain.Select 60 Basic Pain Thresholds greater than 5 seconds and small less than 30 seconds
Mouse, is randomly divided into 6 groups, every group 10, respectively with the cyclobenzaprine hydrochloride spansule of Examples 1 to 3 and comparative example 1~3 with
The dosage of 0.2mgkg~1 is administered, and 1,2,4,8,12,20 and for 24 hours the threshold of pain is being measured after administration, with itself ratio of administration front and back
It maximum may ease pain percentage (possible maximal analgesic%, PMAP) compared with calculating, not occur licking metapedes with 60s
Or stamp metapedes for analgesia a hundred percent, calculation formula is as follows:
As a result as shown in Figure 1.
As can be seen from FIG. 1, the tablet of comparative example 1~3 in interior chip and outer layer due to, without addition sustained release agent, easing pain
Effect is similar with general dual layer piece, occurs peak at 8 hours or so, and analgesic activity fades away after 12 hours, and the application
Examples 1 to 3 has reached sustained release due to being added to crossslinked sodium alginate and chitosan in interior chip and outer layer as sustained release agent
Effect, there is ideal analgesic effect at 4 hours or so in the clad sheet of Examples 1 to 3, and it is small to continue up to 24
Shi Yihou.
Also, by the mutual comparison of Examples 1 to 3 it is found that embodiment 2~3 is only with a kind of analgesic activities
Ingredient cyclobenzaprine hydrochloride or C14H10Cl2NNaO2, PMAP peak is 50% or so, and embodiment 1 is by cyclobenzaprine hydrochloride
It is used in combination with C14H10Cl2NNaO2, PMAP peak produces synergistic function up to 80% or more.
The present invention is described in detail above, specific case used herein is to the principle of the present invention and implementation
Mode is expounded, and the above description of the embodiment is only used to help understand the method for the present invention and its core ideas, including
Best mode, and but also any person skilled in the art can practice the present invention, including any dress of manufacture and use
It sets or system, and implements the method for any combination.It should be pointed out that for those skilled in the art, not
, can be with several improvements and modifications are made to the present invention under the premise of being detached from the principle of the invention, these improvement and modification are also fallen into
In the protection scope of the claims in the present invention.The range of the invention patent protection is defined by the claims, and may include this
Field technical staff it is conceivable that other embodiments.If these other embodiments, which have, is not different from claim text
The structural element of statement, or if they include the equivalent structural elements with the character express of claim without essence difference,
So these other embodiments should also be included in the scope of the claims.
Claims (11)
1. a kind of cyclobenzaprine hydrochloride sustained release preparation, which is characterized in that it is a kind of clad sheet, the group of interior chip become activity at
Divide cyclobenzaprine hydrochloride and C14H10Cl2NNaO2, sustained release agent, diluent, adhesive, disintegrating agent and lubricant, middle layer is sustained release packet
Clothing layer, the composition of outer layer are identical as interior chip.
2. cyclobenzaprine hydrochloride sustained release preparation according to claim 1, which is characterized in that the cyclobenzaprine hydrochloride and double
The weight part ratio of the fragrant sour sodium of chlorine is 1-5:1-10.
3. cyclobenzaprine hydrochloride sustained release preparation according to claim 1, which is characterized in that the weight of the interior chip and outer layer
Amount is than being 3-9:2-6, preferably 3:2.
4. cyclobenzaprine hydrochloride sustained release preparation according to claim 1 or 2, which is characterized in that the sustained release agent is by being crosslinked
The ratio of sodium alginate and chitosan composition, the crossslinked sodium alginate and chitosan is 1-10:1-10.
5. cyclobenzaprine hydrochloride sustained release preparation according to claim 1-3, which is characterized in that the diluent packet
Include one of microcrystalline cellulose, amylum pregelatinisatum, dextrin, mannitol and sorbierite or a variety of.
6. cyclobenzaprine hydrochloride sustained release preparation according to claim 1-3, which is characterized in that described adhesive packet
Include one of starch slurry, methylcellulose, ethyl cellulose, hydroxypropylcellulose and hydroxypropyl methylcellulose or a variety of.
7. cyclobenzaprine hydrochloride sustained release preparation according to claim 1-3, which is characterized in that the disintegrating agent packet
Include one of dried starch, croscarmellose sodium, alginic acid and low-substituted hydroxypropyl cellulose or a variety of.
8. cyclobenzaprine hydrochloride sustained release preparation according to claim 1-3, which is characterized in that the lubricant packet
Include one of talcum powder, magnesium stearate and superfine silica gel powder or a variety of.
9. cyclobenzaprine hydrochloride sustained release preparation according to claim 1, which is characterized in that each component in interior chip and outer layer
Weight are as follows: 1-6 parts of cyclobenzaprine hydrochloride, 1-4 parts of C14H10Cl2NNaO2,15-30 parts of diluent, 2-10 parts of adhesive,
10-20 parts and lubricant 0.1-1 parts of disintegrating agent.
10. cyclobenzaprine hydrochloride sustained release preparation according to claim 1, which is characterized in that the use of the sustained-release coating layer
Amount is 1%-5%.
11. the preparation method of -10 described in any item cyclobenzaprine hydrochloride sustained release preparations according to claim 1, it is characterised in that
The following steps are included:
(1) raw material is weighed by formula rate；
(2) first pressed internal core piece, then be coated, finally suppress clad sheet to get.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811412749.1A CN109316457B (en) | 2018-11-26 | 2018-11-26 | Cyclobenzaprine hydrochloride sustained release preparation and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811412749.1A CN109316457B (en) | 2018-11-26 | 2018-11-26 | Cyclobenzaprine hydrochloride sustained release preparation and preparation method thereof |
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| CN109316457A true CN109316457A (en) | 2019-02-12 |
| CN109316457B CN109316457B (en) | 2021-07-13 |
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| WO2004071497A1 (en) * | 2003-02-11 | 2004-08-26 | Alza Corporation | Methods and dosage forms with modified layer geometry |
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2018
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