Neural microelectrode for electrical stimulation combined with drug release and preparation method thereof

Abstract

The invention discloses a neural microelectrode for electrical stimulation combined with drug release and a preparation method thereof.The neural microelectrode comprises a first flexible substrate layer, a drug-loaded slow-release layer, a second flexible substrate layer, a conductive layer and an insulating covering layer, and the drug-loaded slow-release layer contains chitosan microspheres embedded with drugs; the medicament comprises nerve growth factors and / or anti-inflammatory drugs, a plurality of drug release holes are distributed in the insulating covering layer, an electrode contact is arranged at one end of the conducting layer, a lead connector is electrically arranged at the other end of the conducting layer, and openings for exposing the electrode contact and the lead connector are correspondingly formed in the two ends of the insulating covering layer respectively. According to the neural microelectrode provided by the invention, the drug-loaded slow-release layer is integrated in the neural microelectrode, so that a space for storing a drug does not need to be additionally processed on the membrane layer, and the drug does not need to be additionally loaded, so that the production and processing are relatively convenient and rapid; after the neural microelectrode is implanted into a corresponding tissue in a body, the drug-loaded sustained-release layer can be gradually degraded to slowly release a medicament for repairing nervous tissues or avoiding rejection reaction in a long-acting manner.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of neural microelectrode, and particularly relates to a neural microelectrode for electrical stimulation combined with drug release and a preparation method thereof. BACKGROUND

[0002] The neural microelectrode is an electrophysiological device used for recording or intervening in the state of neural activity, and the implantable neural microelectrode has great potential application value in the fields of medical devices and brain-computer interface. In the medical field, it can be used for the research and treatment of neurological diseases, and in the field of brain-computer interface, it can collect neuron signals with high precision to help paraplegic patients control external devices.

[0003] After being implanted into the target tissue, the implantable neural microelectrode sometimes cannot work normally. The reasons are generally two aspects: one is that the surrounding nerve tissue is obviously damaged during the implantation process, so that the implanted neural microelectrode cannot contact the effective nerve tissue, and thus cannot effectively give stimulation signals or record bioelectric signals; the other is that the implantable neural microelectrode itself has obvious lack of biocompatibility, and after being implanted, a rejection reaction occurs, and the implanted microelectrode is wrapped by sheath fiber tissue, which cannot effectively contact the surrounding nerve tissue. This is also the reason why some implanted microelectrodes can work normally at the beginning but fail after a period of time. The nerve growth factor and anti-inflammatory drugs can make the damaged nerve tissue recover quickly and maintain good activity during the implantation of the neural microelectrode, and at the same time, reduce the rejection reaction. Some neural microelectrodes with drug release function have been disclosed in the prior art, but it is found in actual use that they have many technical problems such as difficulty in processing the drug storage space on the neural microelectrode, difficulty in loading the drug into the storage space, and difficulty in achieving slow release of the drug in the target tissue for a long time. SUMMARY

[0004] The present application provides a neural microelectrode for electrical stimulation combined with drug release and a preparation method thereof, which aims to overcome the above technical problems in the prior art.

[0005] The technical scheme for solving the above technical problems is as follows: a neural microelectrode for electrical stimulation combined with drug release, which comprises a first flexible substrate layer, a drug-loaded slow-release layer, a second flexible substrate layer, a conductive layer and an insulating cover layer which are sequentially stacked from bottom to top, the drug-loaded slow-release layer contains chitosan microspheres embedding a drug, the drug comprises a nerve growth factor and / or an anti-inflammatory drug, the insulating cover layer is distributed with a plurality of drug release holes penetrating downward through the second flexible substrate layer, one end of the conductive layer is electrically connected with an electrode contact, and the other end is electrically connected with a lead connector, and two ends of the insulating cover layer are respectively provided with openings for exposing the electrode contact and the lead connector.

[0006] On the basis of the above technical solutions, the application can further make the following specific or more optimal choices.

[0007] Specifically, the first flexible substrate layer, the second flexible substrate layer and the insulating cover layer are any one of PI film, PET film, Parylene film or PEEK film.

[0008] Specifically, the thickness of the first flexible substrate layer, the second flexible substrate layer and the insulating cover layer is between 1-40 microns.

[0009] Specifically, the thickness of the drug-loaded sustained release layer is 10-20 microns, and the particle size of the chitosan microspheres is 3-10 microns.

[0010] Specifically, the conductive layer is a flexible circuit layer formed by magnetron sputtering and wet etching technology, and the conductive material selected is gold, silver, copper or graphene.

[0011] Specifically, the electrode contact is composed of a conductor protruding from the upper surface of the insulating cover layer, and the conductor is a block-shaped gold, silver, copper, graphene or conductive ink.

[0012] Specifically, the first flexible substrate layer is provided with a number of blank areas not covered by the drug-loaded sustained release layer at the periphery or inside, and the first flexible substrate layer and the second flexible substrate layer are fixedly connected in the blank areas.

[0013] Specifically, the first flexible substrate layer is distributed with a lower through hole, and the lower through hole penetrates the first flexible substrate layer.

[0014] The application also provides a method for preparing the above-mentioned neural microelectrode, which comprises the following steps:

[0015] S1. Chitosan microsphere dispersion liquid preparation: mix and stir the freeze-dried powder of chitosan microspheres embedded with a medicament, polyvinyl alcohol, carboxymethyl chitosan and deionized water according to a weight ratio of 0.3-0.6:0.4-0.6:0.5:6-10, and then mix uniformly to obtain a chitosan microsphere dispersion liquid for standby use;

[0016] S2. Clean and dry the surface of the first flexible substrate layer and then lay it flat as a drug-loaded substrate, use the chitosan microsphere dispersion liquid prepared in S1 as a film-forming liquid to coat and dry the upper surface of the first flexible substrate layer to obtain a drug-loaded sustained release layer;

[0017] S3. depositing the second flexible substrate layer above the drug-loaded sustained-release layer by physical vapor deposition, then depositing a conductive layer on the second flexible substrate layer by magnetron sputtering and wet etching, then depositing an insulating cover layer above the conductive layer by physical vapor deposition, and finally etching the insulating cover layer at a corresponding position to expose both ends of the conductive layer to form the electrode contact and lead joint, and etching a plurality of drug release holes through the insulating cover layer and the second flexible substrate layer at a specific point depth, thereby obtaining the neural microelectrode.

[0018] Specifically, the particle size of the chitosan microspheres is controlled to be 3-10 μm, the drug embedded in the chitosan microspheres includes nerve growth factor and / or anti-inflammatory drugs, and the polyvinyl alcohol is PVA 17-88 or PVA 17-92.

[0019] Compared with the prior art, the neural microelectrode for electrical stimulation combined with drug release has the following beneficial effects:

[0020] The neural microelectrode for electrical stimulation combined with drug release provided by the application has a drug-loaded sustained-release layer integrated inside, and does not need to process a space for storing a drug on each film layer of the microelectrode, nor needs to load a drug into the processed space, so that the production and processing are more convenient and fast. After the neural microelectrode is implanted into a corresponding tissue in the body, tissue fluid enters the drug-loaded sustained-release layer through the drug-loaded hole, so that the drug-loaded sustained-release layer gradually degrades, and the chitosan microspheres and the embedded drug in the drug-loaded sustained-release layer diffuse outward through the drug release hole, thereby achieving the effect of long-acting drug release to quickly restore the damaged nerve tissue, keep the activity, and prevent the sheath fiber tissue from wrapping the neural microelectrode. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 A schematic diagram of the neural microelectrode for electrical stimulation combined with drug release provided by the application (the part below the curve in the figure does not show the insulating cover layer);

[0022] Figure 2 A schematic diagram of the neural microelectrode for electrical stimulation combined with drug release provided by the application (the part below the curve in the figure does not show the insulating cover layer); Figure 1 A schematic diagram of the neural microelectrode for electrical stimulation combined with drug release provided by the application (the part below the curve in the figure does not show the insulating cover layer);

[0023] Figure 3 A schematic diagram of the neural microelectrode for electrical stimulation combined with drug release provided by the application (the part below the curve in the figure does not show the insulating cover layer); Figure 1 A schematic diagram of the neural microelectrode for electrical stimulation combined with drug release provided by the application (the part below the curve in the figure does not show the insulating cover layer);

[0024] Figure 4 A schematic diagram of the neural microelectrode for electrical stimulation combined with drug release provided by the application (the part below the curve in the figure does not show the insulating cover layer); Figure 2 A schematic diagram of the neural microelectrode for electrical stimulation combined with drug release provided by the application (the part below the curve in the figure does not show the insulating cover layer);

[0025] Figure 5 A schematic diagram of the neural microelectrode for electrical stimulation combined with drug release provided by the application (the part below the curve in the figure does not show the insulating cover layer); Figure 4A schematic view of the neural microelectrode shown in the first flexible substrate layer with a lower through hole.

[0026] In the drawings, the components represented by the respective reference numerals are listed as follows:

[0027] 1, first flexible substrate layer; 2, drug-loaded sustained-release layer; 3, second flexible substrate layer; 4, conductive layer; 5, insulating cover layer; 6, drug release hole; 7, electrode contact; 8, lead joint; 9, blank area; 10, lower through hole. DETAILED DESCRIPTION

[0028] The technical solutions provided by the present application will be described in detail below with reference to the drawings and specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0029] In the description of the present application, if the terms indicating the orientation or position relationship such as "up", "down", "left", "right", "top", "bottom", "inside", "outside" are used, the indicated orientation or position relationship is based on the orientation or position relationship shown in the drawings, which is only for the convenience of describing the present application and simplifying the description, and does not indicate or imply that the indicated device or element must have a particular orientation, be constructed and operated in a particular orientation, therefore it cannot be understood as a limitation on the present application.

[0030] As Figures 1 to 5 shown, the present application provides a neural microelectrode for electrical stimulation combined with drug release, which comprises a first flexible substrate layer 1, a drug-loaded sustained-release layer 2, a second flexible substrate layer 3, a conductive layer 4 and an insulating cover layer 5 stacked in order from bottom to top, the drug-loaded sustained-release layer 2 contains chitosan microspheres embedding a medicament, the medicament includes nerve growth factor and / or anti-inflammatory drugs, the insulating cover layer 5 is distributed with a plurality of drug release holes 6 penetrating downward through the second flexible substrate layer 3, one end of the conductive layer 4 is electrically connected with an electrode contact 7, the other end is electrically connected with a lead joint 8, and the two ends of the insulating cover layer 5 are respectively provided with openings for exposing the electrode contact 7 and the lead joint 8.

[0031] It should be noted that the chitosan microspheres embedded with the medicament are prepared according to the technology disclosed in the published Chinese patent CN2012100599428. During the preparation of the chitosan microspheres, one or more of the nerve-nourishing drugs and the glucocorticoids can be added to the solution when the nerve growth factor solution is prepared, the nerve-nourishing drugs including but not limited to vitamin B1, vitamin B2 and mecobalamin, and the glucocorticoids including but not limited to prednisone and dexamethasone. It can be understood that the nerve growth factor can not be contained in the embedded medicament and only the nerve-nourishing drugs or the glucocorticoids can be placed therein according to the requirements.

[0032] In addition, in order to enable the drug-loaded slow-release layer to contain a larger number of chitosan microspheres under the premise of a certain thickness, so as to improve the drug loading capacity and the drug efficacy persistence, the particle size of the chitosan microspheres is preferably controlled in the range of 3-10 μm, and the chitosan microspheres are filtered by a microfiltration membrane after the preparation of the chitosan microspheres is completed, so as to obtain the chitosan microspheres within the above particle size range.

[0033] In an embodiment of the present application, the first flexible substrate layer 1, the second flexible substrate layer 3 and the insulating cover layer 5 are any one of PI film, PET film, Parylene film or PEEK film. The first flexible substrate layer preferably has a thickness of 10-20 μm, the second flexible substrate layer is deposited by a PVD (physical vapor deposition) device and preferably has a thickness of 5-10 μm, and the insulating cover layer preferably has a thickness of 5-20 μm.

[0034] In an embodiment of the present application, the thickness of the drug-loaded slow-release layer 2 is 10-20 μm, and the particle size of the chitosan microspheres is 3-10 μm.

[0035] It should be noted that the drug-loaded slow-release layer is stacked by a plurality of layers of chitosan microspheres embedded with the medicament and is fixed and bonded by the film-forming agent (polyvinyl alcohol and carboxymethyl chitosan). The chitosan, polyvinyl alcohol and carboxymethyl chitosan all have good biocompatibility and will not cause rejection reaction during the drug release, and have good biodegradability and can be degraded and absorbed in the body. The carboxymethyl chitosan not only has a film-forming effect, but also has good water solubility and can be quickly dissolved and released after contacting with tissue fluid, and has the effects of promoting wound healing, analgesia and antibacterial and anti-infection, can quickly promote tissue damage repair and anti-inflammatory effect in the early stage of the implantation of the neural microelectrode, and then the chitosan embedded with the medicament is slowly degraded and releases the drug, so that the effects of early effectiveness and sustained drug release in the middle and late stages are achieved.

[0036] In an embodiment of the present application, the conductive layer 4 is a flexible circuit layer formed by a magnetron sputtering and a wet etching technology, and the conductive material selected is gold, silver, copper or graphene.

[0037] It can be understood that the conductive material is not limited to gold, silver, copper or graphene, and other conductive materials with good conductivity and successfully used in the preparation of neural microelectrodes in practice can be used. The preparation of the conductive layer is not limited to the combination of magnetron sputtering and wet etching technology, and other technologies that can form a metal film layer on an organic film and etch a circuit can also be used.

[0038] In an embodiment of the present application, the electrode contact 7 is composed of a conductor protruding from the upper surface of the insulating cover layer 5, and the conductor is gold, silver, copper, graphene or conductive ink accumulated in a block shape.

[0039] It should be noted that the electrode contact is preferably protruding from the upper surface of the insulating cover layer, in other words, the electrode contact is higher than the upper surface of the insulating cover layer to better contact the neural tissue and transmit electrical signals. The electrode contact can be achieved in various ways, such as printing, accumulating and solidifying conductive ink at the electrode contact position.

[0040] In an embodiment of the present application, as shown in Figure 2 and 4 , the first flexible substrate layer 1 has a plurality of blank areas 9 not covered by the drug-loaded sustained-release layer 2 at the periphery or inside, and the first flexible substrate layer 1 and the second flexible substrate layer 3 are fixedly connected at the blank areas 9.

[0041] It should be noted that the blank area can ensure that the first flexible substrate layer and the second flexible substrate layer are directly adhered, so that after the drug-loaded sustained-release layer is fully released, the first flexible substrate layer can still remain integrated with the neural microelectrode and not fall off.

[0042] In an embodiment of the present application, as shown in Figure 5 , the first flexible substrate layer 1 has a plurality of through holes 10 distributed thereon, and the through holes 10 penetrate the first flexible substrate layer 1.

[0043] It can be understood that the arrangement of the through holes can ensure that the drug-loaded sustained-release layer can be more effectively contacted with the tissue fluid and gradually release the drug after the neural microelectrode is implanted.

[0044] Embodiment 1

[0045] A method for preparing a neural microelectrode, comprising the following steps:

[0046] S1. Preparation of chitosan microsphere dispersion: mix and stir the freeze-dried powder of chitosan microspheres (chitosan microsphere particle size 3-10 μm) embedded with a drug, polyvinyl alcohol (PVA 17-88), carboxymethyl chitosan and deionized water according to a weight ratio of 0.3:0.4:0.5:6, and mix evenly to obtain a chitosan microsphere dispersion for standby;

[0047] S2. The first flexible substrate layer 1 is cleaned and dried, then laid flat as a drug-loading substrate. The chitosan microsphere dispersion prepared in S1 is used as a film-forming liquid to coat and dry on the surface of the first flexible substrate layer 1 to obtain a drug-loading and slow-release layer 2.

[0048] S3. The second flexible substrate layer 3 is deposited on the drug-loading and slow-release layer 2 by physical vapor deposition. Then, the conductive layer 4 is made on the second flexible substrate layer 3 by magnetron sputtering and wet etching. The insulating cover layer 5 is deposited on the conductive layer 4 by physical vapor deposition. Finally, the two ends of the conductive layer 4 are exposed by etching the corresponding positions on the insulating cover layer 5 to form the electrode contact 7 and the lead joint 8. Meanwhile, multiple drug release holes 6 are etched through the insulating cover layer 5 and the second flexible substrate layer 3 at specific point depths, thereby obtaining a neural microelectrode.

[0049] Example 2

[0050] A method for preparing a neural microelectrode, comprising the following steps:

[0051] S1. Preparation of chitosan microsphere dispersion: Chitosan microspheres embedding drug, polyvinyl alcohol (PVA 17-88), carboxymethyl chitosan and deionized water are mixed and stirred according to a weight ratio of 0.4:0.5:0.5:8 to obtain a chitosan microsphere dispersion, which is ready for use.

[0052] S2. The first flexible substrate layer 1 is cleaned and dried, then laid flat as a drug-loading substrate. The chitosan microsphere dispersion prepared in S1 is used as a film-forming liquid to coat and dry on the surface of the first flexible substrate layer 1 to obtain a drug-loading and slow-release layer 2.

[0053] S3. The second flexible substrate layer 3 is deposited on the drug-loading and slow-release layer 2 by physical vapor deposition. Then, the conductive layer 4 is made on the second flexible substrate layer 3 by magnetron sputtering and wet etching. The insulating cover layer 5 is deposited on the conductive layer 4 by physical vapor deposition. Finally, the two ends of the conductive layer 4 are exposed by etching the corresponding positions on the insulating cover layer 5 to form the electrode contact 7 and the lead joint 8. Meanwhile, multiple drug release holes 6 are etched through the insulating cover layer 5 and the second flexible substrate layer 3 at specific point depths, thereby obtaining a neural microelectrode.

[0054] Example 3

[0055] A method for preparing a neural microelectrode, comprising the following steps:

[0056] S1. Preparation of chitosan microspheres dispersion liquid: the chitosan microspheres freeze-dried powder (chitosan microspheres particle size 3-10 μm) embedded with the medicament, polyvinyl alcohol (PVA 17-92), carboxymethyl chitosan and deionized water are mixed and stirred according to the weight ratio of 0.6:0.6:0.5:10, and the chitosan microspheres dispersion liquid is obtained after mixing and stirring, and is ready for use;

[0057] S2. The surface of the first flexible substrate layer 1 is cleaned and dried, and then laid flat as a drug-loaded substrate. The chitosan microspheres dispersion liquid prepared in S1 is used as a film-forming liquid to coat and dry on the surface of the first flexible substrate layer 1 to obtain a drug-loaded sustained-release layer 2;

[0058] S3. The second flexible substrate layer 3 is deposited above the drug-loaded sustained-release layer 2 by physical vapor deposition. Then, the conductive layer 4 is made on the second flexible substrate layer 3 by magnetron sputtering and wet etching. The insulating cover layer 5 is deposited above the conductive layer 4 by physical vapor deposition. Finally, the two ends of the conductive layer 4 are exposed by etching the insulating cover layer 5 at the corresponding position to form the electrode contact 7 and the lead joint 8. At the same time, a plurality of drug release holes 6 are etched through the insulating cover layer 5 and the second flexible substrate layer 3 at a specific point depth. In addition, the bottom surface of the first flexible substrate layer is upward, and a plurality of lower through holes are etched through the drug-loaded sustained-release layer 2 by ion etching technology, thereby obtaining a neural microelectrode.

[0059] It should be noted that in the above preparation method, polyvinyl alcohol and carboxymethyl chitosan mainly play a role in enhancing dispersion when preparing the chitosan microspheres dispersion liquid. In the subsequent drug-loaded sustained-release layer forming process, polyvinyl alcohol and carboxymethyl chitosan mainly play a role in film adhesion. The drug release holes and the lower through holes have the same function, which is mainly to release drugs. The diameters of the two holes are larger than the diameter of the chitosan microspheres. When releasing drugs, part of the chitosan microspheres will first enter the surrounding tissue through the drug release hole or the lower through hole, and then release the drug. The other part will degrade inside the neural microelectrode, and then the drug will diffuse outward through the drug release hole or the lower through hole.

[0060] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A neural microelectrode for electrostimulation combined with drug release, characterized in that, The application relates to a flexible drug delivery device, which comprises, from bottom to top, a first flexible substrate layer (1), a drug-loaded slow-release layer (2), a second flexible substrate layer (3), a conductive layer (4) and an insulating cover layer (5), wherein the drug-loaded slow-release layer (2) contains chitosan microspheres embedding a medicament, the medicament comprises nerve growth factor and / or anti-inflammatory drugs, a plurality of drug release holes (6) are distributed on the insulating cover layer (5) and penetrate through the second flexible substrate layer (3) downwards, one end of the conductive layer (4) is electrically connected with an electrode contact (7), the other end is electrically connected with a lead connector (8), and the two ends of the insulating cover layer (5) are respectively provided with openings for exposing the electrode contact (7) and the lead connector (8).

2. The neural microelectrode for electrostimulation combined with drug release according to claim 1, characterized in that, The first flexible substrate layer (1), the second flexible substrate layer (3) and the insulating cover layer (5) are any one of PI film, PET film, Parylene film or PEEK film.

3. The neural microelectrode for electrostimulation combined with drug release according to claim 1, characterized in that, The thickness of the first flexible substrate layer (1), the second flexible substrate layer (3) and the insulating cover layer (5) is between 1-40 mu m.

4. The neural microelectrode for electrostimulation combined with drug release according to claim 1, characterized in that, The thickness of the drug-loaded slow-release layer (2) is 10-20 mu m, and the particle size of the chitosan microspheres is 3-10 mu m.

5. The neural microelectrode for electrostimulation combined with drug release according to claim 1, characterized in that, The conductive layer (4) is a flexible circuit layer formed by magnetron sputtering and wet etching technology, and the selected conductive material is gold, silver, copper or graphene.

6. The neural microelectrode for electrostimulation combined with drug release according to claim 1, characterized in that, The electrode contact (7) is composed of a conductor protruding from the upper surface of the insulating cover layer (5), and the conductor is block-shaped gold, silver, copper, graphene or conductive ink.

7. The neural microelectrode for electrostimulation combined with drug release according to claim 1, characterized in that, The first flexible substrate layer (1) is provided with a blank area (9) not covered by the drug-loaded slow-release layer (2) on the periphery or inside, and the first flexible substrate layer (1) and the second flexible substrate layer (3) are fixedly connected in the blank area (9).

8. The neural microelectrode for electrostimulation combined with drug release according to any one of claims 1 to 7, characterized in that, The first flexible substrate layer (1) is provided with a lower through hole (10) penetrating through the first flexible substrate layer (1).

9. A method of manufacturing a neural microelectrode according to any one of claims 1 to 8, characterized in that, The application further discloses a preparation method of the flexible drug delivery device, which comprises the following steps: S1. Chitosan microsphere dispersion liquid preparation: chitosan microspheres embedding a medicament, polyvinyl alcohol, carboxymethyl chitosan and deionized water are mixed and stirred according to a weight ratio of 0.3-0.6:0.4-0.6:0.5:6-10, and the mixture is uniformly mixed to obtain the chitosan microsphere dispersion liquid, which is ready for use; S2. The surface of the first flexible substrate layer (1) is cleaned and dried, and then is laid flat as a drug-loaded substrate; the chitosan microsphere dispersion liquid prepared in S1 is used as a film-forming liquid to coat and dry the upper surface of the first flexible substrate layer (1) to obtain the drug-loaded slow-release layer (2). S3. The second flexible substrate layer (3) is deposited above the drug-loaded sustained-release layer (2) by physical vapor deposition, then a conductive layer (4) is made on the second flexible substrate layer (3) by a magnetron sputtering and wet etching process, then an insulating cover layer (5) is deposited above the conductive layer (4) by physical vapor deposition, finally the two ends of the conductive layer (4) are exposed by etching at the corresponding positions on the insulating cover layer (5) to form the electrode contact (7) and the lead joint (8), and a plurality of drug release holes (6) are etched through the insulating cover layer (5) and the second flexible substrate layer (3) at a specific point depth, thus obtaining the neural microelectrode.

10. The method of claim 9, wherein the method further comprises: The particle size of the chitosan microspheres is controlled to be 3-10 μm, and the drugs embedded in the chitosan microspheres include nerve growth factor and / or anti-inflammatory drugs, and the polyvinyl alcohol is PVA 17-88 or PVA 17-92.

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