CN108543215A - A kind of swelling type cross-linked-hyaluronic acid micropin and preparation method thereof - Google Patents
A kind of swelling type cross-linked-hyaluronic acid micropin and preparation method thereof Download PDFInfo
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- CN108543215A CN108543215A CN201810357989.XA CN201810357989A CN108543215A CN 108543215 A CN108543215 A CN 108543215A CN 201810357989 A CN201810357989 A CN 201810357989A CN 108543215 A CN108543215 A CN 108543215A
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- linked
- hyaluronic acid
- micropin
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- swelling type
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0023—Drug applicators using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/02—General characteristics of the apparatus characterised by a particular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2210/00—Anatomical parts of the body
- A61M2210/04—Skin
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Medical Informatics (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a kind of swelling type cross-linked-hyaluronic acid micropins and preparation method thereof, the medicament contg carried which solve the solvable micropin of existing method it is limited and need by import auxiliary can soluble high molecular be administered the technical issues of, swelling type cross-linked-hyaluronic acid micropin is equipped with micropin pedestal and the needle body array that is distributed on pedestal；Each needle body in needle body array is that the cross-linked-hyaluronic acid thick liquid prepared using the molten method of weight is made.The present invention can be used for the preparation field of micropin.
Description
Technical field
The present invention relates to field of medicine preparation, specifically a kind of swelling type cross-linked-hyaluronic acid micropin and its preparation side
Method.
Background technology
Currently, common means of administration has three categories：Oral medication, percutaneous dosing and drug administration by injection.Oral medication is most
Traditional means of administration, patient take simple and convenient, are a kind of most widely used means of administration, but due to liver
First pass effect and the affected part that can not go directly lead to that inefficiency is administered orally；Percutaneous dosing is easy to operate, safe to use, but due to by
The blocking acted on to the stratum corneum barrier of skin, it is difficult to be absorbed by the skin, therefore, it is difficult to reach good effect；And penetrate method
Although dosage is high, work rapid, has the shortcomings that high injection pain, risk, complication and side effect are more.
Micropin as a kind of new percutaneous dosing means due to easy to operate, painless administration, the high advantage of utilization ratio of drug
Cause extensive concern.The micropin type being applied earliest is solid micropin, and follow-up apply is improved by the pretreated method of skin
The drug absorption rate of topical application of drug object, the micropin for being most commonly used for drug release at present is mostly solvable micropin, by dissolved with drug
Soluble high-molecular compound subcutaneously dissolves release drug, but the medicament contg that solvable micropin carries is limited, and needs to pass through
Import auxiliary can soluble high molecular be administered.
Chinese patent (CN104095761A, applicant：Shanghai Hui Lin Pharmaceutical Technology Co., Ltd, the applying date：
2013.04.08 a kind of cross-linked-hyaluronic acid micropin is disclosed in), but does not provide specific preparation method, and for cross-linked transparent
Matter acid micropin gel viscosity relatively low the problems such as micropin can not be prepared by a conventional method, does not elaborate.
Invention content
The present invention is exactly in order to which the medicament contg for solving the solvable micropin carrying of existing method is limited and needs auxiliary by importing
Help can soluble high molecular the technical issues of being administered, a kind of swelling type cross-linked-hyaluronic acid micropin and preparation method thereof is provided,
After micropin is pierced into subcutaneously, cross-linked-hyaluronic acid swelling release drug, and not soluble in water can directly pull out will not remain after swelling
Subcutaneous, while the relatively low micropin needs that can not be prepared by a conventional method of cross-linked-hyaluronic acid micropin gel viscosity can be overcome to set
It counts a kind of new means and destroys cross-linked-hyaluronic acid micropin Gelation Conditions and obtain certain viscosity to prepare micropin.
For this purpose, the present invention provides a kind of swelling type cross-linked-hyaluronic acid micropin, swelling type cross-linked-hyaluronic acid micropin is equipped with
Micropin pedestal and the needle body array being distributed on pedestal；Each needle body in needle body array is the crosslinking prepared using the molten method of weight
Hyaluronic acid thick liquid is made.
Preferably, the weight solvent of thick liquid is the drug solution of one or more solubilities, prepares and carries medicine micropin, drug
A concentration of 1mg/ml~20mg/ml.
Preferably, in the constituent of needle body, cross-linked-hyaluronic acid is that chemical crosslinking or natural crosslinking, crosslinking agent are selected as 1,
4- butanediols and in glycidol ether (BDDE), carbodiimide (EDC), divinylsulfone (DVS), polyvinyl alcohol (PEG) one
Kind is several.
Preferably, in the constituent of needle body, the degree of cross linking of cross-linked-hyaluronic acid is 5%~50%.
Preferably, the raw material for preparing of cross-linked-hyaluronic acid micropin is to destroy cross-linked hyaluronic acid gel item by the molten method of weight
The thick liquid that part obtains.
Preferably, the concrete operations flow of the molten method of weight is to purify cross-linked-hyaluronic acid by 95% alcohol, in unseasoned item
It is redissolved in ultra-pure water under part, obtains cross-linked-hyaluronic acid thick liquid.
Preferably, microneedle preparation method be by cross-linked-hyaluronic acid thick liquid coated on microneedles template by vacuum method by
Step drying prepares cross-linked-hyaluronic acid micropin.
The keratoderma of barrier action is played without penetrating very to drug diffusion since the present invention is only broken through when in use
Cortex, syringe needle do not touch the skin corium of abundant nerve and capillary, thus do not cause pain and sense of discomfort to human body, more
It can be that consumers in general receive, quick, a large amount of release drugs can be haved the function that by the swelling of cross-linked-hyaluronic acid.
Compared with prior art, swelling type cross-linked-hyaluronic acid micropin of the present invention and preparation method thereof solves mesh
The problems such as preceding percutaneous dosing Transdermal absorption difficulty and drug administration by injection pain, the dosage of the solvable micropin of tradition is improved, and be not required to
It delivers other macromolecule soluble polymers and achievees the purpose that drug release.Solves cross-linked-hyaluronic acid due to gel viscosity simultaneously
Low the drawbacks of can not directly preparing micropin, is prepared for cross-linked-hyaluronic acid micropin using the molten method of weight is relatively easy.Therefore, of the invention
Described swelling type cross-linked-hyaluronic acid micropin and preparation method thereof has the advantages that easy to operate, safe and reliable, drugloading rate is high.
Description of the drawings
Fig. 1 is swelling type cross-linked-hyaluronic acid micropin of the present invention and its administration schematic diagram of mechanism；
Fig. 2 is that the present invention carries medicine swelling type cross-linked-hyaluronic acid micropin displaing micro picture；
Fig. 3 is pig skin surfaces pin hole microphoto of the present invention；
Fig. 4 is that micropin operational efficiency of the present invention changes with time figure.
Specific implementation mode
With reference to specific embodiment to swelling type cross-linked-hyaluronic acid micropin of the present invention and preparation method thereof
It is described further, but protection scope of the present invention is not limited to this.
Embodiment 1
Cross-linked-hyaluronic acid is prepared using chemical crosslink technique, the crosslinking agent of the selection glycidol ether for 1,4-butanediol
(BDDE), specific cross-linking method is the NaOH solution for the 0.25mol/l that the non-crosslinked hyaluronic acids of 1g (HA) are dissolved in 9.8ml
In, while 200 μ l crosslinking agent B DDE are added, 2h is reacted under the conditions of 40 DEG C, 100r/min, reaction product is carried with 95% ethyl alcohol
Pure, washing removes the impurity such as crosslinking agent, is dissolved in the Sulforhodamine B of a concentration of 1mg/ml again under the conditions of undried
In (sulforhodamine B) fluorescent solutions, the cross-linked transparent of load Sulforhodamine B (sulforhodamine B) is obtained
Matter acid thick liquid.Swelling type cross-linked-hyaluronic acid micropin and its administration mechanism signal are prepared using the thick liquid that above method obtains
Figure is as shown in Figure 1.
Embodiment 2
By dimethyl silicone polymer and curing agent in mass ratio 10:1 is mixed, and is stirred and is vacuumized removal
Bubble therein；Then the liquid dimethyl silicone polymer containing curing agent of bubble removing will be gone to be cast in horizontal positioned container
It is interior, it is placed in 60 DEG C of baking oven and heats 8 hours to get to solid dimethyl silicone polymer.Then it is taken out from container,
And using laser cutting, microneedles template is prepared using micro-nano processing technology, the template type of selection be it is rectangular, 10 × 10 gusts
Row.
At room temperature, the above-mentioned microneedles template of clean dried is taken, above die cavity at room temperature, fills to prepare in embodiment 1 and bear
Carry the cross-linked-hyaluronic acid thick liquid of Sulforhodamine B (sulforhodamine B), solution to be mixed covers die cavity, at vacuum
Manage 30min；The cross-linked-hyaluronic acid thick liquid for striking off extra load Sulforhodamine B (sulforhodamine B), continues to apply
Unsupported drug thick liquid is applied, continues and handles 30min；Microneedles template is placed in ventilation natural air drying, is demoulded, it is dry.With
It is as shown in Figure 2 that the method obtains load medicine swelling type cross-linked-hyaluronic acid micropin.
Compliance test result
1, external pigskin pierces through test
Smooth fresh porcine skin is lost hair or feathers, the microneedle patch in the embodiment 2 after a piece of drying is taken, by tip alignment pigskin
Surface layer is vertically pierced into, and the back side of the microneedle patch is pressed with hand, the time of pressing is 2min, ensures that swelling type micropin discharges drug
In subcutaneous, micropin to be pulled out and can be observed under an optical microscope, the pig skin surfaces after effect have clearly red pin hole,
His partial skin surface is intact, and pin hole is corresponded with micropin, and red pin hole is aubergine model drug Sulforhodamine B institutes
It stays, shows that the needle body of the microneedle patch can effectively pierce through pigskin surface layer release drug, pig skin surfaces pin hole microphoto such as Fig. 3
It is shown.
2, the subcutaneous release dynamics of drug
For the subcutaneous release dynamics of microneedle patch drug for testing under different durations in embodiment 3, certain amount micropin is taken
Patch, be divided into six groups respectively six groups of microneedle patch of number A, B, C, D, E, F correspond to the durations of different piercing pigskins respectively, point
It Wei not 5min, 10min, 15min, 20min, 25min, 30min：It is pierced into pigskin respectively, collects the microneedle patch after being pierced into pigskin,
Its drug residue is tested with microplate reader, to effective operational efficiency on the porcine skin after being administered, makees micropin administration
The efficiency figure that changes with time is as shown in Figure 4.
Compared with prior art, swelling type cross-linked-hyaluronic acid micropin of the present invention and preparation method thereof solves mesh
The problems such as preceding percutaneous dosing Transdermal absorption difficulty and drug administration by injection pain, the dosage of the solvable micropin of tradition is improved, and be not required to
It delivers other macromolecule soluble polymers and achievees the purpose that drug release.Solves cross-linked-hyaluronic acid due to gel viscosity simultaneously
Low the drawbacks of can not directly preparing micropin, is prepared for cross-linked-hyaluronic acid micropin using the molten method of weight is relatively easy.Therefore, of the invention
The swelling type cross-linked-hyaluronic acid microneedle methods have the advantages that easy to operate, safe and reliable, drugloading rate is high.
Claims (7)
1. a kind of swelling type cross-linked-hyaluronic acid micropin, it is characterized in that the swelling type cross-linked-hyaluronic acid micropin is equipped with micropin bottom
Seat and the needle body array being distributed on pedestal；Each needle body in the needle body array is saturating using the crosslinking of the molten method preparation of weight
Bright matter acid thick liquid is made.
2. swelling type cross-linked-hyaluronic acid micropin according to claim 1, which is characterized in that the weight of the thick liquid is molten
Agent is the drug solution of one or more solubilities, prepares and carries medicine micropin, and drug concentration is 1mg/ml~20mg/ml.
3. swelling type cross-linked-hyaluronic acid micropin according to claim 1, which is characterized in that the constituent of the needle body
In, cross-linked-hyaluronic acid is chemical crosslinking or natural crosslinking, and crosslinking agent is selected as 1,4-butanediol and glycidol ether, carbon two are sub-
One or more of amine, divinylsulfone, polyvinyl alcohol.
4. swelling type cross-linked-hyaluronic acid micropin according to claim 1, which is characterized in that the constituent of the needle body
In, the degree of cross linking of cross-linked-hyaluronic acid is 5%~50%.
5. the preparation method of swelling type cross-linked-hyaluronic acid micropin as described in claim 1, which is characterized in that the crosslinking is saturating
The raw material for preparing of bright matter acid micropin is to destroy the thick liquid that cross-linked hyaluronic acid gel condition obtains by the molten method of weight.
6. the preparation method of swelling type cross-linked-hyaluronic acid micropin according to claim 5, which is characterized in that described heavy molten
The concrete operations flow of method is to purify cross-linked-hyaluronic acid by 95% alcohol, and ultra-pure water is redissolved under the conditions of unseasoned
In, obtain cross-linked-hyaluronic acid thick liquid.
7. the preparation method of swelling type cross-linked-hyaluronic acid micropin according to claim 5, which is characterized in that the micropin
Preparation method is by cross-linked-hyaluronic acid thick liquid coated on by vacuum method, gradually drying prepares cross-linked transparent on microneedles template
Matter acid micropin.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810357989.XA CN108543215A (en) | 2018-04-20 | 2018-04-20 | A kind of swelling type cross-linked-hyaluronic acid micropin and preparation method thereof |
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| CN201810357989.XA CN108543215A (en) | 2018-04-20 | 2018-04-20 | A kind of swelling type cross-linked-hyaluronic acid micropin and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115501474A (en) * | 2022-09-16 | 2022-12-23 | 深圳高性能医疗器械国家研究院有限公司 | Preparation method of soluble microneedle adhesive film |
| WO2023226160A1 (en) * | 2022-05-25 | 2023-11-30 | 迈德科莱(杭州)生物技术有限公司 | Super-swelling microneedle patch, and preparation method therefor and use thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103834053A (en) * | 2014-02-28 | 2014-06-04 | 陕西佰傲再生医学有限公司 | Injectable crosslinked hyaluronic acid gel and preparation method thereof |
| CN107207784A (en) * | 2015-02-13 | 2017-09-26 | (株)安道德玛 | Using cross-linked-hyaluronic acid hydrogel microstructured bodies and its manufacture method |
-
2018
- 2018-04-20 CN CN201810357989.XA patent/CN108543215A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103834053A (en) * | 2014-02-28 | 2014-06-04 | 陕西佰傲再生医学有限公司 | Injectable crosslinked hyaluronic acid gel and preparation method thereof |
| CN107207784A (en) * | 2015-02-13 | 2017-09-26 | (株)安道德玛 | Using cross-linked-hyaluronic acid hydrogel microstructured bodies and its manufacture method |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023226160A1 (en) * | 2022-05-25 | 2023-11-30 | 迈德科莱(杭州)生物技术有限公司 | Super-swelling microneedle patch, and preparation method therefor and use thereof |
| CN115501474A (en) * | 2022-09-16 | 2022-12-23 | 深圳高性能医疗器械国家研究院有限公司 | Preparation method of soluble microneedle adhesive film |
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Application publication date: 20180918 |