CN110680908A - Rapidly disintegrating type A group C meningococcal polysaccharide conjugate vaccine soluble microneedle and preparation method thereof - Google Patents
Rapidly disintegrating type A group C meningococcal polysaccharide conjugate vaccine soluble microneedle and preparation method thereof Download PDFInfo
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- CN110680908A CN110680908A CN201810720838.6A CN201810720838A CN110680908A CN 110680908 A CN110680908 A CN 110680908A CN 201810720838 A CN201810720838 A CN 201810720838A CN 110680908 A CN110680908 A CN 110680908A
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- 108010060123 Conjugate Vaccines Proteins 0.000 title claims abstract description 47
- 229940031670 conjugate vaccine Drugs 0.000 title claims abstract description 47
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/095—Neisseria
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
-
- 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
-
- 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
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/70—Multivalent vaccine
Abstract
The invention provides a rapidly disintegrating type A group C meningococcal polysaccharide conjugate vaccine soluble microneedle, which consists of polyvinylpyrrolidone, a disintegrating agent, superfine calcium carbonate and A group C meningococcal polysaccharide conjugate vaccine; wherein, the solid content of the disintegrating agent in the needle body is 6-16%, the solid content of the superfine calcium carbonate in the needle body is 5-20%, and the solid content of the A group C meningococcal polysaccharide conjugate vaccine in the needle body is not higher than 10%. The soluble microneedle provided by the invention not only improves the drug release rate of the microneedle, but also avoids the technical defect of poor effect of penetrating a needle body into skin caused by rapid drug release; meanwhile, immunological experiment results prove that the microneedle has better immune effect than subcutaneous injection and can effectively generate immune protection effect on organisms.
Description
Technical Field
The invention relates to the technical field of microneedle administration of vaccines, and provides a rapidly disintegrating type A group C meningococcal polysaccharide conjugate vaccine soluble microneedle and a preparation method thereof.
Background
Epidemic cerebrospinal meningitis is purulent meningitis caused by neisseria meningitidis, and is also called epidemic cerebrospinal meningitis. The clinical manifestations include fever, headache, vomiting, skin ecchymosis and stiffness of the neck, and the cerebrospinal fluid is purulent. The epidemic encephalitis vaccines on the market at present are injection preparations, the vaccines are mostly used for children, and the injection preparations have the defect of poor compliance. Therefore, a new administration route of vaccine is urgently needed. Human skin contains abundant antigen presenting cells, for example, Langerhans cells existing in epidermis account for 3-5% of all epidermal cells, so that transdermal immunity has a good research prospect. However, the stratum corneum barrier of the skin makes the delivery of macromolecular drugs problematic.
The soluble micro-needle belongs to a micro-needle type, can overcome the stratum corneum obstacle of human skin, can well promote the transdermal absorption of macromolecular antigen drugs, and realizes painless drug delivery. Different from other microneedles, the soluble microneedles can be dissolved automatically after penetrating into human skin, so that the problems of breakage of intradermal needles of the solid microneedles, small drug-loading amount of coated microneedles and the like are solved, and the method is a popular field for microneedle research at present.
Chinese patent publication No. CN107158368A discloses a soluble microneedle patch containing a polysaccharide conjugate vaccine and a method for preparing the same, which is described in paragraph [ 0042 ] of the document: the needle body of the micro-needle patch can release the target drug into the skin within 15-60 min; and the soluble microneedle body penetrating into the skin part can be ensured to be completely dissolved in the skin and release the A + C group epidemic cerebrospinal meningitis conjugate vaccine into the skin after 30 min. Therefore, when the patient is actually self-administered, the microneedle needs to be continuously pressed on the skin for 30min to be removed, which results in poor patient compliance.
Therefore, it is urgent to develop a soluble microneedle which can completely release the group a and group C meningococcal polysaccharide conjugate vaccine into the skin in a shorter time to overcome the poor patient compliance of the prior art.
At present, no patent document report that a disintegrating agent can be added into a soluble microneedle for quick release of a drug exists, and the applicant of the invention discovers in an earlier preliminary experiment that the disintegrating agent is difficult to effectively penetrate into the skin due to weak mechanical strength of a needle body while the rapid release of the microneedle is improved.
In conclusion, how to develop a rapidly disintegrating type A group C meningococcal polysaccharide conjugate vaccine soluble microneedle can improve the drug release rate of the microneedle after penetrating into the skin and solve the problem of patient compliance; but also can ensure enough mechanical strength to pierce the skin and even improve the immune response effect of the vaccine microneedle, which is a technical problem urgently needed to be solved by the technicians in the field.
Disclosure of Invention
The invention aims to provide a rapidly disintegrating type A group C meningococcal polysaccharide conjugate vaccine soluble microneedle and a preparation method thereof, and solves the bottleneck existing in the prior art by adding a disintegrating agent and superfine calcium carbonate in a proper proportion as a mechanical strength enhancing phase.
In order to realize the research and development thought, the technical scheme adopted by the invention is as follows:
a rapidly disintegrating A group C meningococcal polysaccharide conjugate vaccine soluble microneedle, which consists of polyvinylpyrrolidone, disintegrant, superfine calcium carbonate and A group C meningococcal polysaccharide conjugate vaccine; wherein, the solid content of the disintegrating agent in the needle body is 6-16%, the solid content of the superfine calcium carbonate in the needle body is 5-20%, and the solid content of the A group C meningococcal polysaccharide conjugate vaccine in the needle body is not higher than 10%.
Preferably, the disintegrating agent is selected from one or more of dry starch, sodium carboxymethyl starch, low-substituted cellulose and cross-linked sodium carboxymethyl cellulose,
more preferably, the disintegrant is sodium carboxymethyl starch.
Preferably, the solid content of each component in the needle body is as follows: 70% of PVP, 10% of sodium carboxymethyl starch, 10% of superfine calcium carbonate and 10% of group A and group C meningococcal polysaccharide conjugate vaccine.
The invention also provides a preparation method of the rapidly disintegrating group A and group C meningococcus polysaccharide conjugate vaccine soluble microneedle, namely a dry powder compression molding method is adopted, and the preparation method comprises the following steps: filling the materials with the prescription amount into a female die, punching and demoulding to obtain the flaky microneedle array.
In the invention, the superfine calcium carbonate is used as a mechanical strength enhancing phase, so that the mechanical strength of the microneedle can be greatly improved, and the skin puncture capability of the microneedle can be enhanced.
Compared with the prior art, the soluble microneedle patch of the rapidly disintegrating A-group and C-group meningococcal polysaccharide conjugate vaccine has the innovativeness that:
the microneedle adopts the technology of combining the disintegrant and the superfine calcium carbonate, improves the drug release rate of the microneedle (the drug is completely released within 3 min), and avoids the technical defect of poor effect of the needle body penetrating into the skin caused by rapid drug release; meanwhile, immunological experiment results prove that the microneedle has better immune effect than subcutaneous injection and can effectively generate immune protection effect on organisms.
Detailed Description
In order to make the technical solution of the present invention better understood by those skilled in the art, the technical solution in the present embodiment will be specifically described below. It should be noted that the following examples are only for illustrating the present invention and are not to be construed as limiting the present invention, and any modifications and changes made to the present invention within the spirit and scope of the claims are included in the scope of the present invention.
Example 1: method for preparing soluble microneedle by dry powder compression molding method
The soluble microneedle of the A group and C group meningococcus polysaccharide conjugate vaccine is prepared by the following steps: uniformly mixing the group A and group C meningococcal polysaccharide conjugate vaccine, polyvinylpyrrolidone (PVP), a disintegrating agent and superfine calcium carbonate according to a formula ratio (the average particle size of the materials is less than 0.5 mu m), filling the mixture into a female die with a conical micropore array with fixed specification and size (the array parameters are that the depth of holes is 900 mu m, the diameter of each hole opening is 300 mu m, the distance between the hole arrays is 900 mu m, and 100 holes are formed by 10 multiplied by 10), punching, and demolding to obtain the sheet-shaped microneedle array.
Example 2: effect of different matrix materials on the dissolution rate of microneedle bodies
In order to compare the dissolution rate difference of microneedle bodies made of different matrix materials, several matrix materials, namely polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), polyvinyl alcohol (HA), CMC, methyl vinyl ether-maleic anhydride copolymer (Gantrez) and dextran, were selected for investigation.
0.5% (w.t.) methylene blue was added to prepare a patch-like microneedle array containing no drug according to the method of example 1, and each microneedle was immersed in physiological saline, and the time required for complete dissolution of the needle body was observed with a magnifying glass, and the results are shown in Table 1.
TABLE 1 comparison of dissolution rates of the matrix materials of the needles (mean. + -. SD, n. RTM. 5)
| Needle body matrix material | Time(s) required for complete dissolution of needle body |
| PVP | 20±3 |
| PVA | 205±16 |
| HA | 51±6 |
| CMC | 236±19 |
| Gantrez | 78±8 |
| Dextran | 46±5 |
From the results shown in table 1, the matrix material was preferable to the present invention because PVP dissolves at the highest speed, and the difference in the effects of the other components was further examined.
Example 3: effect of different disintegrants on the dissolution Rate of microneedle bodies
In order to compare the influence of the addition of different disintegrants on the dissolution rate of the microneedle body, the effects of several disintegrants, namely dry starch, sodium carboxymethyl starch, low-substituted cellulose and croscarmellose sodium, are examined.
PVP is used as a needle tip liquid, 0.5% (w.t.) methylene blue is added into a needle body material, and then the disintegrating agents in the table 2 are added, so that the solid content of the final disintegrating agent in the needle body is 10% (w.t.).
A microneedle array was prepared in the form of a sheet without drug by the method of example 1, and the microneedles were immersed in physiological saline to start timing, and the time required for complete dissolution of the needles was observed with a magnifying glass, and the results are shown in Table 2.
Table 2 comparison of dissolution rates of different disintegrants (mean ± SD, n ═ 5)
| Disintegrating agent | Time(s) required for complete dissolution of needle body |
| Control group | 20±3 |
| Dry starch | 17±3 |
| Sodium carboxymethyl starch | 7±1 |
| Low substituted cellulose | 15±2 |
| Croscarmellose sodium | 12±3 |
From the results shown in Table 2, it is understood that 4 kinds of disintegrants have a certain improvement in the dissolution rate of the microneedle body, and among them, sodium carboxymethyl starch is preferable as the present invention, and further the difference in the effects of other components is examined.
Example 4: comparison of skin penetration effect and intradermal dissolution time for microneedles with different mechanically-enhanced phase materials
The microneedle needs proper hardness when penetrating into the skin, and the nano material belongs to one of mechanical reinforcing phases, namely, the polymer-based nano composite material is formed by adding nano particles in organic polymer polymerization of the soluble microneedle so as to reinforce the integral mechanical strength of the microneedle. Regarding the combination of nanomaterials and soluble microneedles, there have been reports in the literature, such as researchers (Yu W, Jiang, Liu D, et al. the simulation of biocidable composite microspheres based on calcium sulfate and gelatin for transdermal delivery of insulin [ J ]. materials science and Engineering: C,2017,71:725-734.) adding a nanomaterial calcium sulfate hemihydrate powder to gelatin to form nanocomposite microneedles, increasing the mechanical strength of the microneedles, making them effective for transdermal delivery of insulin; in addition, researchers (Yan L, Raphael A P, Zhu X, et al, nanocomposite-Strength and dispersing Microneeldedies for Improved transduction Delivery to Human Skin [ J ]. Advanced healthcare materials,2014,3(4):555 and 564.) have added layered double hydroxides to carboxymethyl cellulose to form nanocomposite Microneedles, which also enhance the mechanical strength of the Microneedles, making them effective for Transdermal Delivery of ovalbumin. At present, reports of using superfine calcium carbonate as a soluble microneedle nano-reinforcing phase are not found.
In order to more fully reflect the skin penetrating effect of the soluble microneedles, in this example, referring to example 2 of chinese patent CN107158368A, gelatin was selected as a model of simulated in vitro skin, and the effect difference of three materials, namely, double metal hydroxide, calcium sulfate hemihydrate, and ultrafine calcium carbonate, as the nano-reinforcing phase was examined. A sheet-like microneedle array was fabricated according to the method of example 1, with the proportions of the components in table 3.
The skin penetration depth and dissolution time of the microneedles were also determined by inserting the microneedles into a skin model according to the method described in example 2 of chinese patent CN107158368A, and observing the insertion depth of the microneedles and the time required for the penetration of the microneedles into the skin to be completely dissolved by laser confocal observation, and the results are shown in table 3.
TABLE 3 comparison of skin penetration effect and intradermal dissolution time for different nanoreinforcement phase materials (mean + -SD, n ═ 5)
According to pre-experiments and experiences, the penetration depth of the soluble micro-needle reaches more than 600 μm, and the expected effect of the patent can be achieved only when the dissolving time is less than 5min, so that the use requirement is met. From the results of table 3, it can be seen that:
1) analysis of groups a and B revealed that PVP-blank microneedles could effectively penetrate the skin ex vivo, and after 10% polysaccharide-conjugated vaccine was added, the mechanical properties decreased, the penetration depth decreased greatly to 405 μm, and the intradermal dissolution increased to 18.4min, which is consistent with the description in example 2 of patent CN107158368A, so the content of the vaccine defined in patent CN107158368A could not exceed 8%.
2) Analysis group C revealed that when 10% of disintegrant was added, the penetration depth was further reduced to 316 μm and the dissolution time was reduced to 3.1min, indicating that the disintegrating effect of the disintegrant was also better exerted in the skin, but the mechanical properties of the microneedles were reduced after the disintegrant was added.
3) Analyzing the group D, the group E and the group F, the microneedle penetration depth is improved after different nanometer reinforcing phases are added into the microneedle, but only the group F (added with the superfine calcium carbonate) meets the use requirement; moreover, the microneedle inserted into the skin in the group F can completely disintegrate and release the drug within 3min, and the release speed is far better than that of the microneedle which releases the target drug into the skin within 15-60min and is described in the paragraph [ 0042 ] of the patent CN107158368A, so that the superfine calcium carbonate is selected as the mechanical reinforcing phase material.
Example 5: effect of solid content variation of polysaccharide conjugate vaccine on skin safety
In order to determine the solid content of the A-group and C-group meningococcal polysaccharide conjugate vaccine (hereinafter referred to as polysaccharide conjugate vaccine), the solid contents of carboxymethyl starch sodium and superfine calcium carbonate are assumed to be fixed values, the solid contents of the polysaccharide conjugate vaccine are changed, and the effect difference caused by the change of drug loading is inspected.
Selecting shaved rabbit back skin for microneedle administration, and observing the red and swollen condition of the skin where the microneedle is applied 20min after the microneedle is applied, and finding out that: when the solid content of the polysaccharide conjugate vaccine is within 10%, obvious skin red swelling does not occur, and after the solid content is more than 10%, obvious skin red swelling occurs, and the irritation is high, so the solid content of the polysaccharide conjugate vaccine is not higher than 10%.
Example 6: influence of content change of sodium carboxymethyl starch and superfine calcium carbonate on dissolution speed of microneedle body
On the basis of examples 2 to 5, assuming that the solid content of the polysaccharide conjugate vaccine is a certain value, the influence of the content change of sodium carboxymethyl starch or ultrafine calcium carbonate on the penetration depth and dissolution rate of the microneedle needle body was examined, and the results are shown in table 4.
TABLE 4 solids content range screening of sodium carboxymethyl starch and ultrafine calcium carbonate (mean + -SD, n ═ 5)
According to pre-experiments and experiences, the penetration depth of the soluble micro-needle reaches more than 600 μm, and the expected effect of the patent can be achieved only when the dissolving time is less than 5min, so that the use requirement is met. From the results of table 4, it can be seen that:
1) analysis of groups A to E shows that when the solid contents of the polysaccharide conjugate vaccine and the superfine calcium carbonate are constant values and the content of the sodium carboxymethyl starch is increased from 5% to 17%, the mechanical performance of the microneedle is reduced and the penetration depth of the needle body is gradually reduced; the puncture depth and the dissolution time are comprehensively considered, and when the content of the sodium carboxymethyl starch is 6-16%, the prepared microneedle meets the use requirement.
2) Analysis groups F to I show that when the solid contents of the polysaccharide conjugate vaccine and the sodium carboxymethyl starch are constant values and the content of the superfine calcium carbonate is 5 to 20 percent, the penetration depth and the dissolution time of the prepared microneedle meet the use requirements.
3) The group C is an optimal prescription by comprehensively considering the penetration depth and the dissolution time, namely, the solid content ratio of each component in the microneedle body is as follows: 70% of polyvinylpyrrolidone (PVP), 10% of polysaccharide conjugate vaccine, 10% of sodium carboxymethyl starch and 10% of superfine calcium carbonate.
Example 7: comparison of the immune Effect of mice
Selecting BALB/c female mice of 4-6 weeks old, and setting the adaptive feeding and quarantine period to 3 days. Mice were randomly divided into 6 groups of 6 mice according to the grouping in table 5, and each group was stained with picric acid to distinguish the groups and prevent confusion during feeding and administration. The 6 experimental groups are as follows:
the control group 1 was an injection group of normal saline, 0.2ml was injected subcutaneously at 0,14,28 days, and the injection dose of normal saline was 10 μ g/dose as a blank control;
the injection group is an injection group of polysaccharide conjugate vaccine, 0.2ml is injected subcutaneously in 0,14 and 28 days, and the injection dose of the polysaccharide conjugate vaccine is 10 mu g/dose;
control group 2 was a group of soluble microneedles without polysaccharide conjugate vaccine, prepared according to example 1 as a blank control;
the microneedle set A was a soluble microneedle set containing a polysaccharide conjugate vaccine but not containing sodium carboxymethyl starch and ultrafine calcium carbonate, and the preparation method was as in example 1, with the amount of the polysaccharide conjugate vaccine being 10. mu.g/dose;
the micro-needle group B is a soluble micro-needle group containing polysaccharide conjugate vaccine and sodium carboxymethyl starch but not containing superfine calcium carbonate, and the preparation method refers to example 1, and the dosage of the polysaccharide conjugate vaccine is 10 mu g/dose;
the micro-needle group C is a soluble micro-needle group containing polysaccharide conjugate vaccine, sodium carboxymethyl starch and superfine calcium carbonate, namely an optimal prescription group, and the preparation method refers to example 1, wherein the dosage of the polysaccharide conjugate vaccine is 10 mu g/dose;
the micro-needle group A, B, C was used for depilatory treatment of both sides of the back of the mouse one day before administration, and administered to the depilatory site on the back for 0,14, and 28 days, the sheet-like micro-needle array was pressed onto the skin surface for 3min, and the micro-needles were removed and immunized 3 times in total.
On the 35 th day of immunization, blood was collected from the orbit after removing the eyeball, and after standing at 37 ℃ for 1 hour, the mice were left at 4 ℃ overnight. Placing in a centrifuge, setting rotation speed at 3000rpm, centrifuging for 8min, collecting serum, refrigerating at 2-8 deg.C, separating serum, storing at-20 deg.C, and determining antibody titer by ELISA, wherein the results of each group are shown in Table 5.
Table 5 antibody titer results for each group (mean ± SD, n ═ 6)
| Group of | Group A antibody Titers (mIU/ml) | Group C antibody titer (mIU/ml) |
| Control group 1 | 0 | 0 |
| Control group 2 | 0 | 0 |
| Injection group | 12874±957 | 13609±1077 |
| Micro-needle group A | 754±61 | 681±70 |
| Micro-needle group B | 1378±125 | 1566±138 |
| Micro-needle group C | 37618±2048 | 42893±3189 |
As can be seen from the results of table 5,
1) the micro-needle group A only contains 10% of the vaccine, so that the puncture effect is poor, and the vaccine is only released in a small amount within 3min, so that the antibody titer of the group A is only about 1/17 of the injection group, and the antibody titer of the group C is only about 1/20 of the injection group;
2) the disintegrating agent is added into the micro-needle group B, so the release amount of the vaccine is more than that of the group A, the antibody titer is higher than that of the group A, but the difference is still great compared with that of an injection group;
3) the micro-needle group C contains superfine calcium carbonate and a disintegrating agent, so the penetration effect and the drug release rate are better, the titer of the generated A group antibody is about 2.9 times that of the injection group, and the titer of the C group antibody is about 3.1 times that of the injection group.
In conclusion, the soluble microneedle of the A-group and C-group meningococcal polysaccharide conjugate vaccine prepared by the invention can completely release the drug within 3min after the microneedle is applied, the superfine calcium carbonate can be sufficiently inserted into skin by adding the superfine calcium carbonate, and immunological experiment results prove that the microneedle has an immune effect superior to that of subcutaneous injection and has an obvious effect.
Claims (5)
1. A rapidly disintegrating type soluble microneedle of a group A and group C meningococcal polysaccharide conjugate vaccine is characterized in that the microneedle consists of polyvinylpyrrolidone, a disintegrating agent, superfine calcium carbonate and a group A and group C meningococcal polysaccharide conjugate vaccine; wherein, the solid content of the disintegrating agent in the needle body is 6-16%, the solid content of the superfine calcium carbonate in the needle body is 5-20%, and the solid content of the A group C meningococcal polysaccharide conjugate vaccine in the needle body is not higher than 10%.
2. The rapidly disintegrating group A and group C meningococcal polysaccharide conjugate vaccine soluble microneedle according to claim 1, wherein the disintegrant is one or more selected from dry starch, sodium carboxymethyl starch, low-substituted cellulose, and croscarmellose sodium.
3. The rapidly disintegrating group a and group C meningococcal polysaccharide conjugate vaccine soluble microneedle according to claim 2, wherein the disintegrant is sodium carboxymethyl starch.
4. The rapidly disintegrating group A and group C meningococcal polysaccharide conjugate vaccine soluble microneedle according to any one of claims 1 to 3, wherein the solid content ratio of each component in the microneedle body is: 70% of polyvinylpyrrolidone, 10% of sodium carboxymethyl starch, 10% of superfine calcium carbonate and 10% of A group C meningococcal polysaccharide conjugate vaccine.
5. The method for preparing rapidly disintegrating group A and group C meningococcal polysaccharide conjugate vaccine soluble microneedles in any one of claims 1-3, wherein a dry powder compression molding method is adopted, and the method comprises the following steps: filling the materials with the prescription amount into a female die, punching and demoulding to obtain the flaky microneedle array.
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Citations (4)
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|---|---|---|---|---|
| US20080269685A1 (en) * | 2007-04-16 | 2008-10-30 | Parminder Singh | Solvent-cast microneedle arrays containing active |
| WO2011156641A2 (en) * | 2010-06-09 | 2011-12-15 | Kaspar Roger L | Microneedle arrays for active agent delivery |
| US20170050010A1 (en) * | 2014-04-24 | 2017-02-23 | Georgia Tech Research Corporation | Microneedles and Methods of Manufacture Thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080269685A1 (en) * | 2007-04-16 | 2008-10-30 | Parminder Singh | Solvent-cast microneedle arrays containing active |
| WO2011156641A2 (en) * | 2010-06-09 | 2011-12-15 | Kaspar Roger L | Microneedle arrays for active agent delivery |
| US20170050010A1 (en) * | 2014-04-24 | 2017-02-23 | Georgia Tech Research Corporation | Microneedles and Methods of Manufacture Thereof |
| CN107158368A (en) * | 2017-05-11 | 2017-09-15 | 广州新济药业科技有限公司 | Epidemic meningitis polysaccharide conjugate vaccine solubility microneedle patch and preparation method thereof |
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