CN108451898A - One kind gram vertical boron sieve thermo-sensitive gel agent and its preparation method and application - Google Patents
One kind gram vertical boron sieve thermo-sensitive gel agent and its preparation method and application Download PDFInfo
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- CN108451898A CN108451898A CN201810287388.6A CN201810287388A CN108451898A CN 108451898 A CN108451898 A CN 108451898A CN 201810287388 A CN201810287388 A CN 201810287388A CN 108451898 A CN108451898 A CN 108451898A
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- thermo
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- sensitive gel
- boron sieve
- vertical boron
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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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
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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
- A61K31/69—Boron compounds
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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
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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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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- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of gram vertical boron sieve thermo-sensitive gel agent and its preparation method and application.By percentage to the quality, this gram of vertical boron sieve thermo-sensitive gel agent includes the following raw material component：1% 2% gram vertical boron sieve, 17% 23% poloxamer, 0.1% 1% modified cellulose, 5% 15% propylene glycol and/or glycerine, 5% 10% ethyl alcohol, 0.01% 0.02% dibutyl hydroxy toluene, surplus is water.Gram vertical boron sieve thermo-sensitive gel agent of the present invention can realize injection implantation and long-term drug release.Using percutaneous drug delivery mode, so that drug is played good slow releasing function in human body, and drug extravasation can be prevented, releases the drug for a long time.
Description
Technical field
The present invention relates to a kind of gram vertical boron sieve thermo-sensitive gel agent and its preparation method and application, belong to pharmaceutical technology field.
Background technology
Eczema is the allergic inflammation dermatoses caused by a variety of internal and external factors, multiform damage symmetrical with skin lesion,
Acute pruritus has and oozes out tendency, recurrent exerbation etc. for notable feature.The illness is touching refractory, and clinical treatment is intractable, to patient's
Physical and mental health causes large effect.
Currently, western medicine is with Loratadine, glucocorticoid medicine and convergence, protection class pharmaceutical preparation etc. pair
Based on disease treatment, though these drugs can control symptom, easily recurred after being discontinued, and it is long-term, repeatedly, large area use can cause to suffer from
The adverse reactions such as the telangiectasis of person part, cutaneous pigmentation.
Gram vertical boron sieve is non-hormone drug, has the advantages such as easy to use, adverse reaction is small, recurrence rate is low, have compared with
High clinical value.It is huge therefore, it is possible to the market demand for the treatment of gram vertical boron sieve of eczema.
Invention content
In view of the problems of the above-mentioned prior art, the purpose of the present invention is to propose to a kind of gram vertical boron sieve thermo-sensitive gel agent
And its preparation method and application.This gram of vertical boron sieve thermo-sensitive gel agent can realize injection implantation and long-term drug release.
The purpose of the present invention is achieved by the following technical programs：
A kind of gram vertical boron sieve thermo-sensitive gel agent, by percentage to the quality, this gram of vertical boron sieve thermo-sensitive gel agent include following former
Expect component：
Gram vertical boron sieve of 1%-2%, the modified cellulose of the poloxamer of 17%-23%, 0.1%-1%, 5%-15%
Propylene glycol and/or glycerine, 5%-10% ethyl alcohol, the dibutyl hydroxy toluene of 0.01%-0.02%, surplus is water.
In above-mentioned gram vertical boron sieve thermo-sensitive gel agent, the effect of poloxamer is temperature sensitive material, in the prior art can
There is provided the poloxamer branch compound of temperature sensitive performance can be used in gram vertical boron sieve thermo-sensitive gel agent that this specification is recorded；
Preferably, the poloxamer includes poloxamer188 and PLURONICS F87；Wherein, with a gram institute for vertical boron sieve thermo-sensitive gel agent
It is 100% meter to have raw material components, and the content of poloxamer188 can be 16wt%-20wt%, and the content of PLURONICS F87 can
Think 1%-3%.
In above-mentioned gram vertical boron sieve thermo-sensitive gel agent, the effect of modified cellulose is to increase viscosity, when increasing skin delay
Between.Therefore, the group modified cellulose that can increase viscosity of routine may be incorporated for this specification record in the prior art
Gram vertical boron sieve thermo-sensitive gel agent.Preferably, the modified cellulose includes that hydroxypropyl cellulose, ethyl cellulose and methyl are fine
Tie up the combination of one or more of element.
The thermo-sensitive gel material of the present invention can change with environment temperature and certain phase transformation occurs, and can realize injection implantation
So that drug is played good slow releasing function in human body using percutaneous drug delivery mode with long-term drug release, drug extravasation is prevented, when long
Between release the drug, advantageously than similar skin dosage form.
The present invention also provides the preparation methods of above-mentioned gram vertical boron sieve thermo-sensitive gel agent comprising following steps：
By the water mixing of poloxamer, modified cellulose and partial amount, the first mixture is obtained after swelling；
Gram vertical boron sieve, ethyl alcohol and propylene glycol and/or glycerine mixed dissolution are obtained into the second mixture；
By the water mixing of the first mixture, the second mixture, dibutyl hydroxy toluene and remainder component to get to gram vertical
Boron sieve thermo-sensitive gel agent.
In above-mentioned preparation method, it is preferred that by the water mixing of poloxamer, modified cellulose and partial amount, after swelling
The step of obtaining the first mixture include：
The surface that poloxamer and modified cellulose are interspersed among to the water of partial amount, after stirring and evenly mixing, it is small that refrigeration places 10
When more than, that is, complete swelling, obtain the first mixture.
In above-mentioned preparation method, it is preferred that by the water mixing of poloxamer, modified cellulose and partial amount, after swelling
The step of obtaining the first mixture include：
The surface that poloxamer and modified cellulose are interspersed among to the water of partial amount, after stirring and evenly mixing, it is small that refrigeration places 24
When, that is, swelling is completed, the first mixture is obtained.
In above-mentioned preparation method, it is preferred that the temperature of refrigeration is 0-4 degree.
The present invention also provides above-mentioned gram vertical boron sieve thermo-sensitive gel agent answering in the drug as treatment allergic dermatitis
With.
In the present invention, gram vertical boron sieve thermo-sensitive gel agent can inject implantation, and because of the semisolid of gelling agent because being fluid
Change trend characteristic, can release the drug for a long time, also be not easy from skin to extravasation.
The present invention protrusion effect be：
Gram vertical boron sieve thermo-sensitive gel agent of the present invention can realize injection implantation and long-term drug release.Using percutaneous drug delivery side
Formula makes drug play good slow releasing function in human body, and can prevent drug extravasation, releases the drug for a long time.
Description of the drawings
Fig. 1 is the gel buildup release rate and time chart of embodiment 6.
Specific implementation mode
In order to which technical characteristic, purpose and the advantageous effect to the present invention are more clearly understood, now to the skill of the present invention
Art scheme carry out it is described further below, but should not be understood as to the present invention can practical range restriction.Institute in following embodiments
Experimental method is stated, is conventional method unless otherwise specified；The reagent and material unless otherwise specified can be from business ways
Diameter obtains.
Embodiment 1
The present embodiment provides a kind of gram vertical boron sieve thermo-sensitive gel agent, are prepared in fact by following method：
(1) poloxamer188 17g is taken, PLURONICS F87 3g, it is pure that 0.5 gram of hydroxypropyl cellulose is dispersed evenly to 40g
Watermeter face places for 24 hours, is statically placed in refrigerator and refrigerates after being sufficiently stirred, and is completely dissolved fully swelling and is used as the first mixture；
(2) by 2g grams of vertical boron sieve, 10g propylene glycol and 10g alcohol mixeding liquids, stirring and dissolving, as the second mixture；
(3) the second mixture is added while stirring in the first mixture, finally plus purified water is to 100g, stirs evenly and obtains
Thermo-sensitive gel for treating allergic dermatitis.
Embodiment 2
The present embodiment provides a kind of gram vertical boron sieve thermo-sensitive gel agent, are prepared in fact by following method：
(1) poloxamer188 17g is taken, PLURONICS F87 3g, it is pure that 0.5 gram of methyl base cellulose is dispersed evenly to 40g
Watermeter face places for 24 hours, is statically placed in refrigerator and refrigerates after being sufficiently stirred, and is completely dissolved fully swelling and is used as the first mixture；
(2) by 2g grams of vertical boron sieve, 15g propylene glycol and 10g alcohol mixeding liquids, stirring and dissolving, as the second mixture；
(3) the second mixture is added while stirring in the first mixture, finally plus purified water is to 100g, stirs evenly and obtains
Thermo-sensitive gel for treating allergic dermatitis.
Embodiment 3
The present embodiment provides a kind of gram vertical boron sieve thermo-sensitive gel agent, are prepared in fact by following method：
(1) poloxamer188 17g is taken, PLURONICS F87 3g, it is pure that 0.5 gram of ethyl base cellulose is dispersed evenly to 40g
Watermeter face places for 24 hours, is statically placed in refrigerator and refrigerates after being sufficiently stirred, and is completely dissolved fully swelling and is used as the first mixture；
(2) by 2g grams of vertical boron sieve, 10g propylene glycol and 10g alcohol mixeding liquids, stirring and dissolving, as the second mixture；
(3) the second mixture is added while stirring in the first mixture, finally plus purified water is to 100g, stirs evenly and obtains
Thermo-sensitive gel for treating allergic dermatitis.
Embodiment 4
The present embodiment provides a kind of gram vertical boron sieve thermo-sensitive gel agent, are prepared in fact by following method：
(1) poloxamer188 18.5g, PLURONICS F87 2.5g, 0.5 gram of hydroxypropyl cellulose is taken to be dispersed evenly to
40g purifies water surface, places for 24 hours, is statically placed in refrigerator and refrigerates after being sufficiently stirred, and is completely dissolved fully swelling as the first mixing
Object；
(2) by 2g grams of vertical boron sieve, 10g propylene glycol and 10g alcohol mixeding liquids, stirring and dissolving, as the second mixture；
(3), the second mixture is added while stirring in the first mixture, finally plus purified water is to 100g, stirs evenly to obtain the final product
To the thermo-sensitive gel for treating allergic dermatitis.
Embodiment 5
The present embodiment provides a kind of gram vertical boron sieve thermo-sensitive gel agent, are prepared in fact by following method：
(1) poloxamer188 18.5g, PLURONICS F87 2.5g, 0.5 gram of hydroxypropyl cellulose is taken to be dispersed evenly to
40g purifies water surface, places for 24 hours, is statically placed in refrigerator and refrigerates after being sufficiently stirred, and is completely dissolved fully swelling as the first mixing
Object；
(2) by 2g grams of vertical boron sieve, 10g glycerine and 10g alcohol mixeding liquids, stirring and dissolving, as the second mixture；
(3), the second mixture is added while stirring in the first mixture, finally plus purified water is to 100g, stirs evenly to obtain the final product
To the thermo-sensitive gel for treating allergic dermatitis.
Embodiment 6
Gram vertical boron sieve thermo-sensitive gel agent (by taking embodiment 1 as an example) and existing gram of vertical boron sieve obtained by above-described embodiment is soft
Cream carries out contrast experiment.Existing gram of vertical boron sieve ointment can be with reference to related art scheme in CN101160124 according to conventional system
It is standby, commercially available gram of vertical boron sieve ointment can also be bought.
Gram vertical boron sieve thermo-sensitive gel agent and ointment are placed in the interior centrifuge tube for containing 30ml PBS (pH=7.4) buffer solution,
Centrifuge tube is placed on 37 DEG C of shaking baths of constant temperature, and shaking table carries out reciprocating vibration with 100rpm, in sampling 1ml in the stipulated time, and
Supplement 1ml PBS solutions detect after sample liquid filtration through HPLC in centrifuge tube immediately, are released by standard curve converted score and calculating
Put rate.The results are shown in Figure 1 for it, and in figure, F2 is gram vertical boron sieve gel of the embodiment of the present invention, and F1 is that gram vertical boron sieve of purchase is soft
Cream.As seen from Figure 1, the release rate of gram vertical boron sieve gel of the invention is significantly less than control ointment, shows apparent sustained release
Effect.
As it can be seen that gram vertical boron sieve thermo-sensitive gel agent of the present invention can realize injection implantation and long-term drug release.It is given using skin
Prescription formula makes drug play good slow releasing function in human body, and can prevent drug extravasation, releases the drug for a long time.
Claims (8)
1. a kind of gram vertical boron sieve thermo-sensitive gel agent, by percentage to the quality, this gram of vertical boron sieve thermo-sensitive gel agent includes the following raw material
Component：
Gram vertical boron sieve of 1%-2%, the modified cellulose of the poloxamer of 17%-23%, 0.1%-1%, the third of 5%-15%
The ethyl alcohol of glycol and/or glycerine, 5%-10%, the dibutyl hydroxy toluene of 0.01%-0.02%, surplus are water.
2. according to claim 1 gram of vertical boron sieve thermo-sensitive gel agent, it is characterised in that：The poloxamer includes that pool Lip river is husky
Nurse 407 and PLURONICS F87；Wherein, it is poloxamer in terms of 100% by gram all raw material components of vertical boron sieve thermo-sensitive gel agent
407 content is 16wt%-20wt%, and the content of PLURONICS F87 is 1%-3%.
3. according to claim 1 gram of vertical boron sieve thermo-sensitive gel agent, it is characterised in that：The modified cellulose includes hydroxypropyl
The combination of one or more of base cellulose, ethyl cellulose and methylcellulose.
4. the preparation method of the vertical boron sieve thermo-sensitive gel agent of claim 1-3 any one of them gram comprising following steps：
By the water mixing of poloxamer, modified cellulose and partial amount, the first mixture is obtained after swelling；
Gram vertical boron sieve, ethyl alcohol and propylene glycol and/or glycerine mixed dissolution are obtained into the second mixture；
By the water mixing of the first mixture, the second mixture, dibutyl hydroxy toluene and remainder component to get to gram vertical boron sieve
Thermo-sensitive gel agent.
5. preparation method according to claim 4, wherein by the water mixing of poloxamer, modified cellulose and partial amount,
The step of the first mixture is obtained after swelling include：
The surface that poloxamer and modified cellulose are interspersed among to the water of partial amount, after stirring and evenly mixing, refrigeration place 10 hours with
On, that is, swelling is completed, the first mixture is obtained.
6. preparation method according to claim 5, wherein by the water mixing of poloxamer, modified cellulose and partial amount,
The step of the first mixture is obtained after swelling include：
The surface that poloxamer and modified cellulose are interspersed among to the water of partial amount, after stirring and evenly mixing, refrigeration placement 24 hours, i.e.,
Swelling is completed, the first mixture is obtained.
7. preparation method according to claim 5 or 6, wherein the temperature of refrigeration is 0-4 degree.
8. the vertical boron sieve thermo-sensitive gel agent of claim 1-3 any one of them gram is in the drug as treatment allergic dermatitis
Using.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810287388.6A CN108451898A (en) | 2018-04-03 | 2018-04-03 | One kind gram vertical boron sieve thermo-sensitive gel agent and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810287388.6A CN108451898A (en) | 2018-04-03 | 2018-04-03 | One kind gram vertical boron sieve thermo-sensitive gel agent and its preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108451898A true CN108451898A (en) | 2018-08-28 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810287388.6A Withdrawn CN108451898A (en) | 2018-04-03 | 2018-04-03 | One kind gram vertical boron sieve thermo-sensitive gel agent and its preparation method and application |
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| Country | Link |
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| CN (1) | CN108451898A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109464381A (en) * | 2018-12-29 | 2019-03-15 | 广州迈康药业科技有限公司 | Gram vertical boron sieve cubic liquid crystal gel preparation and preparation method thereof |
| CN113712977A (en) * | 2020-05-25 | 2021-11-30 | 南京帝昌医药科技有限公司 | Cliboroluo external preparation and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101160124A (en) * | 2005-02-16 | 2008-04-09 | 安纳考尔医药公司 | Boron-containing small molecules |
| CN102784169A (en) * | 2011-05-19 | 2012-11-21 | 王成 | In situ gel preparation loaded with Kangfuxin and its preparation method and use |
| WO2017102565A1 (en) * | 2015-12-15 | 2017-06-22 | Rita Dobmeyer | Pharmaceutical composition comprising a fulvic acid and at least one boron-containing compound |
-
2018
- 2018-04-03 CN CN201810287388.6A patent/CN108451898A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101160124A (en) * | 2005-02-16 | 2008-04-09 | 安纳考尔医药公司 | Boron-containing small molecules |
| CN102784169A (en) * | 2011-05-19 | 2012-11-21 | 王成 | In situ gel preparation loaded with Kangfuxin and its preparation method and use |
| WO2017102565A1 (en) * | 2015-12-15 | 2017-06-22 | Rita Dobmeyer | Pharmaceutical composition comprising a fulvic acid and at least one boron-containing compound |
Non-Patent Citations (1)
| Title |
|---|
| REMA ZEBDA ET AL.: "Phosphodiesterase 4 inhibitors", 《J AM ACAD DERMATOL》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109464381A (en) * | 2018-12-29 | 2019-03-15 | 广州迈康药业科技有限公司 | Gram vertical boron sieve cubic liquid crystal gel preparation and preparation method thereof |
| CN109464381B (en) * | 2018-12-29 | 2021-12-28 | 广州迈康药业科技有限公司 | Kelibong Roche liquid crystal gel preparation and preparation method thereof |
| CN113712977A (en) * | 2020-05-25 | 2021-11-30 | 南京帝昌医药科技有限公司 | Cliboroluo external preparation and preparation method and application thereof |
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Application publication date: 20180828 |